SCI - Neurology Flashcards

Question

26. Regarding neoplastic spinal cord disease, which of the following is incorrect? a. Malignancies that may metastasize to the spine include those arising from the breast, lung, prostate, and kidney b. Radiation therapy can improve pain and neurologic symptoms in patients with lymphoproliferative neoplasia producing cord compression c. High-dose 24-hour treatment of continuous IV methylprednisolone is the treatment of choice d. Intradural extramedullary tumors causing cord compression include neurofibromas, schwannomas, and meningiomas e. Intramedullary tumors include ependymomas and astrocytomas

Answer 1

26. c Neoplastic disease of the spinal cord can be intrinsic to the cord or metastatic disease. Tumors affecting the spinal column and spinal cord can be anatomically divided into extradural or intradural, the latter further classified into intramedullary or extramedullary. All of these tumors can also be divided into metastatic or nonmetastatic disease. The most common nonmetastatic extramedullary tumors include neurofibromas, schwannomas, and meningiomas. The most frequent nonmetastatic intramedullary tumors are spinal cord astrocytomas and ependymomas. Metastatic disease to the spinal cord most commonly originates from breast, lung, prostate, and kidney cancer, although it is not limited to these. Other invading neoplastic lesions include lymphoma and multiple myeloma. Spinal cord neoplastic disease usually presents with pain and focal neurologic manifestations resulting from spinal cord compression or dysfunction. Patients have findings consistent with myelopathy, along with other manifestations of the underlying cancer. The diagnostic test of choice to determine the presence of neoplastic disease is MRI of the spinal cord with gadolinium. There are multiple treatment options that are selected depending on the underlying neoplasm, degree of neurologic disease, timing of presentation, functional status, and prognosis. Steroids are frequently used, especially in the acute phase of cord compression, with dexamethasone being the most commonly used. Methylprednisolone with a 30 mg/kg bolus and an infusion of 5.4 mg/kg/hour for 23 hours is a formulation used more commonly in spinal cord traumatic injury, but not for neoplastic disease. Radiation therapy is used for radiosensitive neoplasias, such as lymphoproliferative disease and germ cell tumors, and for various types of metastases, particularly in the setting of cord compression. It may be used as a palliative measure to improve symptoms of pain and other symptoms of cord compression. Surgical resection should be entertained when feasible, even in cases of metastatic disease, where it has shown superiority when combined with radiotherapy as compared to radiotherapy alone. However surgical treatments may not be possible in some neoplasms, such as in intramedullary lesions. Bradley WG, Daroff RB, Fenichel GM, et al. Neurology in Clinical Practice, 5th ed. Philadelphia, PA: Elsevier; 2008. Ecker RD, Endo T, Wetjen NM, et al. Diagnosis and treatment of vertebral column metastases. Mayo Clinic Proc. 2005; 80:1177–1186. Ropper AH, Samuels MA. Adams and Victor’s Principles of Neurology, 9th ed. New York: McGraw-Hill; 2009.

Answer 2

27. e Spinal cord trauma is a significant cause of myelopathy and common cause of severe disability after trauma, especially in young adults. Trauma produces spinal cord injury by multiple mechanisms, including direct transection of the cord, displacement of spinal column structures, disruption of axons, interruption of blood flow to the cord, hemorrhage, inflammation, and/or edema. After spinal cord injury there are two phases: an initial phase of spinal shock followed by a second phase of increased reflex activity with spasticity. The acute spinal shock phase occurs soon after the injury and lasts for a few weeks (between 1 and 6, but with no exact limits). It is manifested by suppression of spinal segmental activity below the level of the lesion. With complete spinal cord injury, the patient has a flaccid weakness with areflexia below the lesion, atonic bladder with overflow incontinence, distention of the bowel with absence of peristalsis and constipation, depressed rectal tone, and abolished genital reflexes. There is autonomic dysfunction below the lesion explaining the labile blood pressure seen in these cases. A few weeks after spinal cord injury, the patient will start presenting features of increased reflexic activity below the lesion. There is no clear chronologic boundary between this stage and the previous one of spinal shock. In this second stage, there are upper motor neuron findings with increased tone, leading to spasticity and hyperreflexia. Plantar responses are upgoing; triple flexion response commonly occurs. Patients will have detrusor spasms and hyperactivity with urinary loss secondary to spontaneous bladder contraction as well as spontaneous reflex defecation. These bladder and bowel reflexes are probably explained by the lack of inhibition of the sacral neurons by rostral centers, leading to spontaneous contraction secondary to a local reflex arc. Neither spontaneous reflex defecation nor detrusor contraction are present in the spinal shock phase. Ropper AH, Samuels MA. Adams and Victor’s Principles of Neurology, 9th ed. New York: McGraw-Hill; 2009.

Answer 3

28. e Superficial siderosis of the CNS is the result of hemosiderin deposition in the subpial layers of the brain and spinal cord, which is secondary to recurrent bleeding into the subarachnoid space. The bleeding source is undetermined in most cases. Some risk factors have been reported, such as previous subarachnoid hemorrhage, head trauma, and previous intradural surgery; however, the significance of these historical aspects is not clear. The most common manifestations include gait ataxia, dysarthria, and sensorineural hearing loss. Other clinical manifestations include anosmia, cognitive decline, and myelopathic findings. Xanthochromia and/or the presence of red blood cells is a common CSF finding. MRI shows T2 hypointensity around the brain, brain stem, and spinal cord, and sometimes intraspinal fluid collections are detected. If a possible etiology for the recurrent bleeding is found, endovascular or surgical repair may be entertained; however, it is unclear if this approach has a significant impact on progression of the disease. Kumar N, Cohen-Gadol AA, Wright RA, et al. Superficial siderosis. Neurology. 2006; 66:1144–1152.

Answer 4

29. a Syphilis is caused by the spirochete Treponema pallidum and is associated with a wide variety of neurologic manifestations. Myelopathy is frequently encountered and can be produced by various mechanisms, including spinal cord infarction. Tabes dorsalis is the classic myelopathic syndrome described in neurosyphilis. Tabes dorsalis is characterized by dysfunction of the posterior columns with prominent sensory ataxia and proprioceptive loss, along with other manifestations such as sphincter dysfunction, L’hermitte’s sign, lancinating pain, and areflexia. The natural history of tabes dorsalis has been described in three different phases: * The preataxic phase in which the patient has lancinating pain of his legs, along with sphincter and sexual dysfunction * The ataxic phase with prominent proprioceptive loss, sensory ataxia leading to the development of Charcot joints * The postataxic or paralytic phase characterized by spastic paraparesis, autonomic dysfunction, worsening of the pain and sphincter dysfunction, and cachexia Pathologic findings demonstrate inflammation, demyelination, and gliosis of the posterior columns and dorsal roots of the spinal cord. Syphilis can also produce spinal cord disease by other mechanisms, such as spinal cord infarction from vasculitis, meningomyelitis manifested as an inflammatory transverse myelitis, hypertrophic pachymeningitis, and gummas, which can be intramedullary or extramedullary. The treatment of neurosyphilis is penicillin G intravenously, with a dose of 24 million units daily in divided doses for 14 days. Ropper AH, Samuels MA. Adams and Victor’s Principles of Neurology, 9th ed. New York: McGraw-Hill; 2009.

Answer 5

30. a The conus medullaris is at the lower end of the spinal cord, beyond which the lumbar and sacral spinal nerve roots descend within the spinal canal as a bundle of fibers, called the cauda equina (meaning horse’s tail), to reach their corresponding exit foramina. Lesions in the lumbar or lumbosacral region can compress either the conus medullaris and/or the cauda equina, producing a distinctive clinical syndrome. A lesion affecting primarily the conus medullaris presents with perineal sensory deficit in a saddle distribution, which is usually bilateral and symmetric. Pain is often symmetric, but is not typically radicular. There is usually lower extremity symmetric weakness and sometimes decreased or absent ankle reflexes, but this may be mild. Bowel and bladder dysfunction occur early in the course of the disease, as well as sexual dysfunction. A lesion that affects the cauda equina presents with distinctive radicular pain and sensory loss with an asymmetric distribution. Motor deficits are also asymmetric with evidence of hyporeflexia. Bowel and bladder function may be affected, but usually this occurs later in the course and less frequently than with conus lesions. Spasticity and other upper motor neuron signs will not be present as this is a lower motor neuron disorder. This patient has features of cauda equina syndrome. This condition is produced by compression or irritation of the fibers, with causes including disc herniations, tumors, hematomas, or trauma, as well as infectious and inflammatory disorders (e.g., tuberculosis, cytomegalovirus, and sarcoidosis). There are no clinical features to suggest an intramedullary tumor, transverse myelitis, or an epidural hematoma. Brazis PW, Masdeu JC, Biller J. Localization in Clinical Neurology, 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2007. Ropper AH, Samuels MA. Adams and Victor’s Principles of Neurology, 9th ed. New York: McGraw-Hill; 2009.

Answer 6

31. e The diagnosis of amyotrophic lateral sclerosis (ALS) is made on the basis of the history, examination, and electrophysiologic testing. The El-Escorial diagnostic criteria for definite ALS as defined by the World Federation of Neurology include clinical and/or electrophysiologic evidence of both upper and lower motor neuron involvement in at least three of the four following regions: bulbar, cervical, thoracic, and lumbosacral. Electrodiagnostic features of ALS include evidence of ongoing denervation indicated by the presence of spontaneous activity (fibrillation potentials) and chronic denervation (reduced recruitment and polyphasic motor units). Other variable features include fasciculation potentials and motor unit instability (variability of motor unit amplitude and presence of repetitive discharges). Reduced motor unit recruitment with a rapid firing rate on EMG reflects compensation of existing motor units for those that are no longer functional, and only a single motor unit may be seen to be activated during voluntary contraction in a severely denervated muscle. Sensory NCS are normal. EMG/NCS is indicated in the evaluation of a patient with suspected ALS, and should include evaluation of cervical, thoracic, and lumbosacral regions routinely, and of bulbar region when clinically affected. The differential diagnosis of ALS is broad, and investigations into alternative, especially treatable, causes are indicated when there are features suggesting the possibility of another diagnosis. In the evaluation of an ALS patient, laboratory and imaging studies are done as indicated to exclude mimickers of ALS. There are a variety of other disorders that lead to clinical signs and symptoms of both upper and lower motor neuron involvement that are on the differential diagnosis of ALS, including Machado-Joseph disease (spinocerebellar ataxia type 3), adrenoleukodystrophy, multifocal motor neuropathy, hyperparathyroidism, cervical spondylosis, GM2 gangliosidoses, polyglucosan body disease, paraneoplastic motor neuron disease, HIV-associated motor neuron disease, West Nile virus infection, and others. Laboratory tests may include evaluation of parathyroid hormone, paraneoplastic autoantibodies (such as anti-Hu), GM1 autoantibodies, and others depending on the suspicion. MRI of the brain and spinal cord are indicated to exclude other potential causes masquerading clinically as ALS, such as cervical spondylosis. MRI in ALS may show increased signal in the corticospinal tract on T2-, proton density-, and FLAIR-weighted images, possibly due to Wallerian degeneration. Bradley WG, Daroff RB, Fenichel GM, et al. Neurology in Clinical Practice, 5th ed. Philadelphia, PA: Elsevier; 2008. 32. a Copper is a trace element that functions as a prosthetic group in metalloenzymes that have a role in maintaining the structure and function of the CNS. Copper deficiency causes a myelopathy similar to that seen in vitamin B12 deficiency. It also produces multiple other neurologic manifestations, including peripheral neuropathy, CNS demyelination, myopathy, and optic neuropathy. Hematologic manifestations are also seen in copper deficiency, with anemia, neutropenia, and left shift in granulocytic and erythroid maturation. MRI of the spine may show T2-signal hyperintensity in the paramedian cord, most frequently in the cervical region. Copper deficiency results from malabsorption, one of the most common causes being previous gastric surgery, especially bariatric surgery for weight loss. It is frequent to find vitamin B12 deficiency along with copper deficiency, and in most cases in clinical practice, vitamin B12 is supplemented, whereas copper is usually overlooked. Lack of improvement with vitamin B12 supplementation should prompt evaluation for copper deficiency. Excessive zinc ingestion may also contribute to copper deficiency, because zinc induces the synthesis of metallothionein in enterocytes, which has a high affinity to copper, leading to internalization of copper into the enterocytes and its eventual loss when they are sloughed off from the mucosa. Kumar N. Copper deficiency myelopathy (Human Swayback). Mayo Clin Proc. 2006; 81(10):1371–1384. Ropper AH, Samuels MA. Adams and Victor’s Principles of Neurology, 9th ed. New York: McGraw-Hill; 2009.

Answer 7

32. a Copper is a trace element that functions as a prosthetic group in metalloenzymes that have a role in maintaining the structure and function of the CNS. Copper deficiency causes a myelopathy similar to that seen in vitamin B12 deficiency. It also produces multiple other neurologic manifestations, including peripheral neuropathy, CNS demyelination, myopathy, and optic neuropathy. Hematologic manifestations are also seen in copper deficiency, with anemia, neutropenia, and left shift in granulocytic and erythroid maturation. MRI of the spine may show T2-signal hyperintensity in the paramedian cord, most frequently in the cervical region. Copper deficiency results from malabsorption, one of the most common causes being previous gastric surgery, especially bariatric surgery for weight loss. It is frequent to find vitamin B12 deficiency along with copper deficiency, and in most cases in clinical practice, vitamin B12 is supplemented, whereas copper is usually overlooked. Lack of improvement with vitamin B12 supplementation should prompt evaluation for copper deficiency. Excessive zinc ingestion may also contribute to copper deficiency, because zinc induces the synthesis of metallothionein in enterocytes, which has a high affinity to copper, leading to internalization of copper into the enterocytes and its eventual loss when they are sloughed off from the mucosa. Kumar N. Copper deficiency myelopathy (Human Swayback). Mayo Clin Proc. 2006; 81(10):1371–1384. Ropper AH, Samuels MA. Adams and Victor’s Principles of Neurology, 9th ed. New York: McGraw-Hill; 2009.

Answer 8

33. e This patient’s history and examination are consistent with Kennedy’s disease (X-linked spinobulbar muscular atrophy). Kennedy’s disease typically presents in males beginning the fourth decade of life. The clinical presentation includes motor weakness often starting in proximal muscles associated with features of lower motor neuron dysfunction, such as atrophy and hyporeflexia. Tremor, muscle cramps, and fasciculations, particularly involving the face and perioral region, are other features. Later in the course of the disease, evidence of bulbar dysfunction becomes apparent. Examination may reveal gynecomastia, but its absence does not preclude this diagnosis. Endocrine abnormalities, including hypogonadism with sterility and diabetes, occur in some patients. This disorder rarely manifests in females, likely due to random X-inactivation, but has been reported, presenting with bulbar dysfunction. Kennedy’s disease results from expansion of a CAG repeat in the androgen receptor protein gene on the X chromosome. Genetic testing for this disorder is commercially available. Treatment is supportive. Bradley WG, Daroff RB, Fenichel GM, et al. Neurology in Clinical Practice, 5th ed. Philadelphia, PA: Elsevier; 2008.

Answer 9

34. b The spinal cord lies dorsal to the posterior longitudinal ligament. The vertebral column is composed of vertebral bodies, pedicles, and laminae. Two pedicles arise from the posterior aspect of each vertebral body. Two laminae fuse posteriorly leaving the spinal canal in the middle within which the spinal cord lies. Multiple ligaments attach and give support to the vertebral column. The anterior longitudinal ligament runs along the anterior surface of the vertebral bodies, whereas the posterior longitudinal ligament runs along the posterior surface and ventral to the spinal cord. The ligamentum flavum runs in the posterior aspect of the spinal canal, and the denticulate ligament extends on both sides of the spinal cord between the pia mater and the dura mater. Between each vertebral body there is an intervertebral disc, which is composed of a central nucleus pulposus and a surrounding annulus fibrosus. The spinal cord has 31 segments and a corresponding number of pairs of spinal nerve roots, with 8 cervical, 12 thoracic, 5 lumbar, 5 sacral, and 1 coccygeal. The cervical nerve roots exit the spinal column above the vertebral body of the same number, except for C8, which exit between the C7 and T1 intervertebral foramen. The subsequent nerve roots below this level exit the spinal column below the corresponding vertebral body. In adults, the spinal cord extends from the foramen magnum to the level of L1 to L2. It has two major enlargements, one in the cervical region and another one in the lumbosacral region. These enlargements correlate with the areas related to innervation of the arms and legs. Blumenfeld H. Neuronatomy through Clinical Cases, 1st ed. Sunderland, MA: Sinauer Associates; 2002. Ropper AH, Samuels MA. Adams and Victor’s Principles of Neurology, 9th ed. New York: McGraw-Hill; 2009.

Answer 10

35. a This patient’s history and muscle biopsy are consistent with spinal muscular atrophy (SMA) type 1. The SMAs are a group of four disorders of anterior horn cell degeneration. SMA type 1, infantile SMA, or Werdnig-Hoffman disease presents with decreased fetal movements, neonatal hypotonia, and weak cry. Patients with SMA type 1 exhibit head lag and frog-leg posture when supine, and are never able to sit up or achieve anti-gravity strength in the arms or legs. Diffuse areflexia is often present. Bulbar involvement leads to dysphagia, and respiratory involvement occurs. Death usually occurs by 2 years of age. In SMA type 2, intermediate SMA, symptoms begin in the first 1 to 2 years of life, with motor delay and tremor in some cases. This form is less severe than SMA type 1, with most children being able to sit unsupported, but significant contractures develop, and most are not able to ambulate. SMA type 3, juvenile SMA or Kugelberg-Welander disease, typically presents in childhood (between ages 5 and 15 years) with difficulty walking. The clinical picture is one of proximal muscle weakness, a fine action tremor, and fasciculations. Patients often remain ambulatory into adulthood. SMA type 4, adult-onset SMA or pseudomyopathic SMA, is the least common and least severe. Symptoms typically begin in the third to fourth decades of life and include proximal muscle weakness, with the quadriceps being prominently involved, and fasciculations. Ambulation into late adulthood is common. Cranial nerve and respiratory involvement is rare. Commercially available molecular analysis of the survival motor neuron (SMN) gene is available. Serum creatine kinase may be significantly elevated (more than 10 times normal), particularly in the younger-onset forms. Sensory NCS are normal; EMG shows evidence of acute and chronic denervation and reinnervation, with large polyphasic motor units. Complex repetitive discharges occur in SMA type 3. Muscle biopsy shows atrophy of the entire fascicles or groups of fascicles, with normal or hypertrophied neighboring fascicles, as depicted in Figure 11.5. The majority of cases of SMA are due to mutations in the SMN1 gene on chromosome 5. Inheritance is autosomal recessive in most cases, though a minority of cases involving other genes with autosomal dominant or X-linked inheritance have been identified. The gene product, SMN1 protein, is involved in RNA processing. In later-onset forms, some residual functional protein is present, leading to the milder phenotype. As mentioned, SMA type 4 presents in adulthood. Charcot-Marie-Tooth type 1 typically presents in childhood (rather than the neonatal period), and will not be associated with the muscle biopsy findings shown in Figure 11.5. Congenital myasthenia and botulism are on the differential diagnosis of neonatal hypotonia but would not lead to the muscle biopsy findings shown in Figure 11.5. Aminoff MJ. Neurology and General Medicine, 4th ed. Philadelphia, PA: Elsevier; 2008. Bradley WG, Daroff RB, Fenichel GM, et al. Neurology in Clinical Practice, 5th ed. Philadelphia, PA: Elsevier; 200

Answer 11

36. e This patient has nitrous oxide toxicity, causing a neurologic manifestation that has been termed “anesthesia paresthetica.” Nitrous oxide is an inhalational anesthetic agent that produces irreversible oxidation of cobalamin and makes the methylcobalamin inactive. The manifestations occur in patients with underlying cobalamin deficiency even after a single exposure to nitrous oxide, usually with a rapid onset of symptoms. However, chronic exposure can lead to similar manifestations, and this has been described among anesthetists, dentists, or medical personnel working with nitrous oxide, either from occupational exposure or from abuse. Patients with chronic exposure can have an acute exacerbation during an acute exposure to larger amounts of nitrous oxide. The neurologic manifestations include myelopathy, neuropathy, or even cognitive changes and encephalopathy. MRI changes with T2 hyperintensity can be detected. Prophylactic vitamin B12 can help prevent this condition. This patient does not have copper deficiency, which usually produces a more protracted course, usually related to malabsorption. In cases of malabsorption after gastric bypass, the manifestations usually occur gradually over months or years. Folate deficiency causes neurologic manifestations in very rare instances, and usually gradually over long periods of time in patients who have other nutrient deficiencies. In cases of spinal epidural abscess or hematomas causing myelopathy, the MRI images usually are distinct, showing spinal cord compression, which is not the case in this patient. Kinsella LJ, Green R. “Anesthesia paresthetica”: Nitrous oxide-induced cobalamin deficiency. Neurology. 1995; 45:1608–1610. Kumar N. Copper deficiency myelopathy (Human Swayback). Mayo Clin Proc. 2006; 81:1371–1384. Ropper AH, Samuels MA. Adams and Victor’s Principles of Neurology, 9th ed. New York: McGraw-Hill; 2009.

Answer 12

37. c This patient has Hirayama disease, also known as monomelic amyotrophy. This condition presents in young patients of Asian origin, and it is characterized by progressive asymmetric wasting of one or both hands and forearms. Examination shows atrophy and fasciculations with no sensory deficits. These patients have a high incidence of atopic disorders. The pathophysiology is not understood, but some have suggested a chronic progressive compression of the cervical cord, associated with dynamic changes of the cervical dural sac and spinal cord induced by neck flexion. MRI of the cervical spine in flexion demonstrates cervical cord thinning with signal changes. A cervical collar may be used to prevent neck flexion, and surgical intervention may have an impact in some patients. Amyotrophic lateral sclerosis (ALS) is a progressive degenerative motor neuron disease in which there are upper and lower motor neuron signs in multiple segments of the neuraxis. This patient has only lower motor neuron findings in his upper extremities, which is usually not consistent with ALS. Primary lateral sclerosis is a disorder in which the predominant feature is the presence of upper motor neuron signs, without lower motor neuron signs, which is not consistent with the case depicted. Spinal muscular atrophy is a group of genetic disorders that affect the anterior horn cells of the spinal cord and motor nuclei of the brain stem. Usually there are findings affecting upper and lower limbs, as well as bulbar muscles. This patient is not in the age group and does not have other clinical features to suggest the diagnosis of cervical osteoarthritis. Fenichel GM. Clinical Pediatric Neurology: A Signs and Symptoms Approach, 6th ed. Philadelphia, PA: Saunders Elsevier; 2009. Hirayama K. Juvenile muscular atrophy of distal upper extremity (Hirayama disease). Inter Med. 2000; 39:283–290. Ropper AH, Samuels MA. Adams and Victor’s Principles of Neurology, 9th ed. New York: McGraw-Hill; 2009.

Answer 13

38. e This patient has a spinal cord infarction in the territory of the anterior spinal artery. The spinal cord’s blood supply consists of one anterior spinal artery and two posterior spinal arteries. The former supplies the anterior two-thirds of the spinal cord, whereas the two posterior spinal arteries supply the posterior one-third. Therefore patients with an anterior spinal artery syndrome present with weakness below the lesion, with sensory deficit to pain and temperature due to involvement of the lateral spinothalamic tracts, but because the dorsal columns are not involved, there is preservation of vibratory sense and proprioception. Spinal cord infarction may occur after aortic aneurysm surgical repair. Endovascular approaches have a lower rate of overall complications as compared to open surgical approaches, including lower rates of spinal cord ischemia. In this case there is no history or clinical findings to support a spinal epidural hematoma as the cause. Patients with copper and vitamin B12 deficiency usually present rather gradually and not rapidly as in this case. Furthermore, vitamin B12 deficiency is associated with posterior column degeneration affecting proprioception and vibratory sensation, which was not present in this case. Patients with vitamin B12 deficiency are at risk for nitrous oxide toxicity. Ropper AH, Samuels MA. Adams and Victor’s Principles of Neurology, 9th ed. New York: McGraw-Hill; 2009.

Answer 14

39. d This patient most likely has a spinal epidural abscess. This condition occurs when an infectious process extends into the epidural space, either from local extension or from a remote source via hematogenous spread. Risk factors include diabetes mellitus, intravenous drug use, previous infection, history of spine injury or spine surgery, renal disease, and multiple medical comorbidities. The most common presenting symptoms are fever, low back pain, and progressive neurologic symptoms attributed to cord or root compression. Myelopathic findings develop over time, and patients may have upper motor neuron findings below the level of the lesion. Sometimes the patient worsens rapidly and examination may show findings of spinal shock. The symptoms may ascend over time as the epidural abscess propagates cranially. MRI of the spine is the standard test for diagnosis and has high sensitivity. An LP is not usually performed, and may be contraindicated due to risk of spread of infection to the intrathecal compartment. Furthermore, CSF cultures are positive only in 25% of cases. The most common organism is S. aureus, followed by streptococci, gram-negative bacilli, and anaerobic organisms. Empiric broad-spectrum antibiotics should be started early, with narrowing of the spectrum once a specific organism is identified. The usual duration of antibiotic therapy is between 4 and 6 weeks; however, antibiotics alone may not be effective. Once this condition is suspected, urgent neurosurgical consultation should be obtained. If the patient has findings of cord compression, surgical evacuation should be performed. Epidural spinal abscess is a true neurosurgical and neurologic emergency. Ropper AH, Samuels MA. Adams and Victor’s Principles of Neurology, 9th ed. New York: McGraw-Hill; 2009.

Answer 15

64. c This patient has a spinal dural arteriovenous fistula (DAVF), which is the most common type of spinal vascular malformation. This lesion can be fed by one or multiple arteries and is a low pressure and low flow vascular lesion. DAVF is more frequent in men and above 50 years of age. The typical location is in the lower thoracic and lumbar regions, and this type of lesion rarely produces hemorrhage. Patients present with pain, weakness, and sensory symptoms below the level of the lesion. The myelopathic syndrome is usually gradually progressive and caused by venous hypertension and congestion. MRI of the spine shows enlargement of the cord with hyperintensity on T2 seen over several levels, with intradural flow voids suggesting this pathology (Figure 2.19). Spinal angiogram is the gold standard diagnostic test to detect this abnormality. Treatment involves angiographic embolization and/or surgical removal of the lesion. The radiographic findings in this case are consistent with an expanding lesion with T2 hyperintensity in the cord. The presentation is gradually progressive and consistent with DAVF. Epidural hematoma and spinal cord infarct have a more acute presentation and do not show the MRI findings seen in this case. This is not a cavernous malformation or a venous angioma, which are not common in this location. Bradley WG, Daroff RB, Fenichel GM, Jankovic J. Neurology in Clinical Practice, 5th ed. Philadelphia, PA: Elsevier; 2008.

Answer 16

6a. Opioid receptors are a group of G-protein coupled receptors, with opioids acting as ligands. The endogenous opioids are dynorphins, enkephalins, endorphins, endomorphins, and ORL1. There are four major subtypes of opioid receptors. The first is δ, including subtypes δ1 and δ2. They are involved with analgesia, antidepressant effects, and physical dependence. The second is κ and includes κ1, κ2, and κ3. These are involved in spinal analgesia, sedation, miosis, and inhibition of antidiuretic hormone release. The third is μ and includes μ1, μ2, and μ3. The subtype μ1 is involved in supraspinal analgesia and physical dependence; μ2 is involved in respiratory depression, miosis, euphoria, reduced gastrointestinal motility, and physical dependence. The actions of μ3 are not clear. The fourth is ORL1/orphanin, which is involved in anxiety, depression, appetite, and development of tolerance to μ agonists.

Answer 17

22. e, 23. c This patient has copper deficiency related to excess zinc intake. This can be related to excess dietary intake (as in this case), overuse of denture cream, parenteral feeding deficiency, and gastrointestinal surgery. This syndrome occurs because zinc increases enterocyte metallothionein synthesis. These excess enterocyte metallothioneins easily bind copper. The resultant excessively bound copper within the enterocytes is then excreted when the enterocytes are sloughed off, resulting in impaired absorption. Copper deficiency myelopathy syndrome resembles the subacute combined degeneration seen with vitamin B12 deficiency. Copper deficiency causes a sensorimotor peripheral neuropathy with axonal loss features on electrodiagnostic studies combined with myelopathy in the form of spastic paraparesis and posterior column dysfunction. Pancytopenia is also frequently associated. Copper deficiency is discussed also in Chapter 11. The history of excess zinc makes this more likely than vitamin B12 deficiency in this particular patient. Vitamin E deficiency can mimic symptoms of spinocerebellar ataxia, which is not present in this patient. Goodman BP, Bosch EP, Ross MA, et al. Clinical and electrodiagnostic findings in copper deficiency myeloneuropathy. J Neurol Neurosurg Psychiatry. 2009; 80:524–547. Kumar N, Gross JB Jr, Ahlskog JE. Copper deficiency myelopathy produces a clinical picture like subacute combined degeneration. Neurology. 2004; 63:33–39.

Answer 18

24. e, 25. a This patient’s neurologic findings are likely the result of vitamin E deficiency related to chronic diarrhea and subsequent malabsorption of fat-soluble vitamins, that is, vitamins D, A, K, and E. These vitamins need to be supplemented, especially vitamin E as in this case. Symptoms resemble a spinocerebellar ataxia syndrome such as Friedrich ataxia and may include ataxia, dysarthria, areflexia, extensor plantar responses, and large fiber sensory loss. Presentation can occur at any age in the setting of chronic diarrhea and malabsorption diseases. Vitamin E deficiency is more likely to occur in childhood when a genetic etiology is present, such as α-tocopherol-transfer protein mutation or abetalipoproteinemia (Bassen-Kornzweig syndrome). Abetalipoproteinemia is caused by a mutation of a microsomal triglyceride transfer protein resulting in absence of apolipoprotein B–containing proteins. Laboratory findings show low vitamin E levels. Acanthocytosis may also be seen on peripheral smear. See discussion to question 22 for copper deficiency, and that to question 27 for vitamin B12 deficiency. Bradley WG, Daroff RB, Fenichel GM, et al. Neurology in Clinical Practice, 5th ed. Philadelphia, PA: Elsevier; 2008. Ropper AH, Samuels MA. Adams and Victor’s Principles of Neurology, 9th ed. New York, NY: McGraw-Hill; 2009. Satya-Murti S, Howard L, Krohel G, et al. The spectrum of neurologic disorder from vitamin E deficiency. Neurology. 1986; 36:917–921.

Answer 19

26. c Extensor plantar responses would not be seen in thiamine (vitamin B1) deficiency. This deficiency would be more likely to cause peripheral neuropathy and flexor plantar responses. Thiamine deficiency in Wernicke-Korsakoff syndrome is discussed in question 10. Thiamine deficiency causes an axonal, sensorimotor peripheral neuropathy with weakness and distal sensory loss. This is termed “dry beriberi.” When it is associated with cardiac involvement in the form of cardiomegaly, cardiomyopathy, congestive heart failure, arrhythmia and tachycardia, and peripheral edema, it is called “wet beriberi.” Thiamine deficiency has also been reported to cause Leigh syndrome (Leigh subacute necrotizing encephalomyelopathy). Laboratory findings may include decreased serum thiamine, erythrocyte transketolase activity and urinary thiamine, with increased pyruvate and lactate levels, in addition to characteristic electrodiagnostic findings. Bradley WG, Daroff RB, Fenichel GM, et al. Neurology in Clinical Practice, 5th ed. Philadelphia, PA: Elsevier; 2008. Pincus JH. Subacute necrotizing encephalomyelopathy (Leigh’s disease): a consideration of clinical features and etiology. Dev Med Child Neurol. 1972; 14:87–101. Tanphaichitr V. In: Shils M (Ed), Modern Nutrition in Health and Medicine, 9th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2000.

Answer 20

27. d The neurologic deficits in vitamin B12 (cobalamin) deficiency are ultimately related to a defect in methionine production. Vitamin B12 is a cofactor for methionine synthase, which is involved in conversion of homocysteine to methionine and production of succinyl-CoA from methylmalonyl-CoA. Methionine is subsequently a precursor for S-adenosyl-l-methionine, which helps with methylation of myelin basic protein. Without this process, abnormal myelin structure results in neurologic deficit. The syndrome resulting from vitamin B12 deficiency is called subacute combined degeneration because of sensorimotor peripheral neuropathy combined with myelopathy, spastic paraparesis and posterior column dysfunction. Complete blood cell count may reveal a macrocytic anemia. Occasionally, vitamin B12 levels may be in the low normal or even normal range despite true deficiency. If clinical suspicion is present for deficiency, the levels of metabolic intermediaries homocysteine and methylmalonic acid should be checked, both of which would be elevated in vitamin B12 deficiency. Animal products (meat and dairy) provide the primary dietary source of vitamin B12 for humans. This puts older adults, alcoholics, patients with malnutrition, and strict vegans at high risk for development of deficiency. Bradley WG, Daroff RB, Fenichel GM, et al. Neurology in Clinical Practice, 5th ed. Philadelphia, PA: Elsevier; 2008. Green R, Kinsella LJ. Current concepts in the diagnosis of cobalamin deficiency. Neurology. 1995; 45(8):1435–1440. Hemmer B, Glocker FX, Schumacher M, et al. Subacute combined degeneration: clinical, electrophysiological, and magnetic resonance imaging findings. J Neurol Neurosurg Psychiatry. 1998; 65:822–827. Lindenbaum J, Savage DG, Stabler SP, et al. Diagnosis of cobalamin deficiency, II: relative sensitivities of serum cobalamin, methylmalonic acid, and total homocysteine concentrations. Am J Hematol. 1990; 34:99–107.

Answer 21

28. d, 29. b This patient exhibits symptoms consistent with arsenic poisoning. Arsenic is a naturally occurring element most commonly incorporated into organic or inorganic compounds, both of which are very toxic. It can also occur in gas form. With acute exposure, symptoms may develop within minutes to hours and usually begin with gastrointestinal symptoms such as abdominal pain, nausea, vomiting, and diarrhea. A garlic odor on the breath is characteristic. These symptoms can be followed by hypotension, dehydration, and cardiac and respiratory instability. Delirium, encephalopathy, coma, and seizures may occur. Other acute manifestations include proteinuria, hematuria, and acute tubular necrosis. If patients survive, within 1 to 3 weeks, they can develop hepatitis, pancytopenia, and a symmetric sensorimotor peripheral neuropathy, which typically begins with distal paresthesias, followed rapidly by an ascending sensory loss and weakness, which mimics Guillain-Barré syndrome. The neuropathy can progress to intense burning pain, especially in the soles. In addition, dermatologic lesions can occur and may include alopecia, oral mucosal ulcerations, diffuse pruritic macular rash, and scaly rash on the palms and soles. A dry hacking cough and Mees lines (horizontal 1- to 2-mm white lines on the nails) may also occur. In chronic poisoning, the peripheral neuropathy and dermatologic symptoms are usually more prominent than the gastrointestinal symptoms. Cancers of the liver, bladder, kidney, skin, lung, nasal mucosa, and prostate have been reported with chronic exposure. After a suspected acute ingestion of arsenic, abdominal radiographs may reveal gastrointestinal radiopaque material. Urine arsenic levels are preferable to blood arsenic levels, but both can be used. Fish or shellfish intake within the previous 48–72 hours can cause falsely elevated levels of arsenic. For chronic exposure, hair and nail samples can be analyzed for the presence of arsenic, and 24-hour urine arsenic or spot urine arsenic and creatinine levels can be checked. Additional evaluations should include renal and liver function tests, complete blood cell count, urinalysis, and electrodiagnostic testing if there are symptoms of peripheral neuropathy. A distal sensorimotor axonopathy is the typical finding. Acute treatment includes fluid and electrolyte replacement, cardiac monitoring, activated charcoal, and chelation therapy. Chelation agents typically used include dimercaprol (British Anti-Lewisite) and meso-2,3-dimercaptosuccinic acid (succimer). Although symptoms can mimic Guillain-Barré syndrome, the constellation of clinical symptoms and signs described and adequate evaluation should have ruled this out. Cyanide and mercury poisoning are discussed in questions 30 and 31 respectively. Thallium causes acute gastrointestinal symptoms, confusion, painful (mostly sensory) neuropathy with autonomic features, and alopecia, which classically occurs about 2 to 4 weeks after ingestion. Danan M, Dally S, Conso F. Arsenic-induced encephalopathy. Neurology. 1984; 34:1524. Flomenbaum N, Goldfrank L, Hoffman R, et al. Goldfrank’s Toxicologic Emergencies, 8th ed. New York, NY: McGraw-Hill; 2006. Windebank AJ. Arsenic. In: Spencer PS, Schaumburg HH (Eds), Experimental and Clinical Neurotoxicology. New York, NY: Oxford University Press; 2000. Yip L, Dart RC. Arsenic. In: Sullivan JB, Krieger GR (Eds), Clinical Environmental Health and Toxic Exposures. Philadelphia, PA: Lippincott Williams & Wilkins; 2001.

Answer 22

37. c This patient describes symptoms most consistent with botulism, likely related to foodborne source from home canning. Botulism is a potentially life-threatening neuroparalytic syndrome resulting from exposure to botulinum toxin, produced by Clostridium botulinum. There are at least eight distinct types of botulinum toxin, although the most commonly involved is botulinum toxin A. There are multiple forms of botulism including foodborne botulism (ingestion of food contaminated by botulinum toxin), wound botulism (infection of a wound by C. botulinum, with subsequent production of neurotoxin), infantile botulism (ingestion of clostridial spores that then colonize the gastrointestinal tract and release toxin), adult enteric infectious botulism (toxin produced in the gastrointestinal tract), and inhalational botulism (aerosolized toxin related to acts of bioterrorism). Botulinum toxin binds to the synaptotagmin II receptor on presynaptic cholinergic synapses and neuromuscular junctions. After the heavy chain of the toxin binds to the receptors, the light chain translocates into the nerve cell via endocytosis. Upon entering the cytoplasm, the toxin irreversibly inhibits acetylcholine release by cleaving various proteins involved in neuroexocytosis of acetylcholine. Botulinum toxin A and E cleave SNAP-25; botulinum toxin C cleaves SNAP-25 and syntaxin; and botulinum B, D, F, and G cleave synaptobrevin. Reversal of this inhibition requires sprouting of a new presynaptic terminal and formation of a new synapse. This generally takes 3 to 6 months. Although the toxin can be quite harmful, these effects are used for therapeutic purposes, such as for the treatment of dystonia, spasticity, and other neurologic disorders. Symptoms related to foodborne botulism may begin within 12 to 36 hours after ingestion of the toxin but may be delayed for several days. Symptoms include acute onset of multiple cranial neuropathies, blurred vision (due to fixed pupillary dilation), symmetric descending weakness, urinary retention, and constipation. Gastrointestinal symptoms such as diarrhea, abdominal pain, nausea, and vomiting often precede neurologic symptoms in foodborne botulism. Symptoms are not consistent with myasthenia gravis (there is no diurnal variation or other historical points to suggest fatigability; discussed in Chapter 10), Lambert-Eaton myasthenic syndrome (discussed in Chapter 10), or Guillain-Barré syndrome (which presents with ascending, not descending, weakness and without pupillary involvement; discussed in Chapter 9). He has no history of cancer and is otherwise healthy, making leptomeningeal carcinomatosis unlikely, especially with the abrupt onset of symptoms. Abrutyn E. Botulism. In: Fauci AS, Isselbacher KJ, Braunwald E, et al. (Eds), Principles of Internal Medicine, 14th ed. New York, NY: McGraw-Hill; 1998. Hughes JM, Blumenthal JR, Merson MH, et al. Clinical features of types A and B food-borne botulism. Ann Intern Med. 1981; 95:442–445. Jin R, Rummel A, Binz T, et al. Botulinum neurotoxin B recognizes its protein receptor with high affinity and specificity. Nature. 2006; 444(7122):1019–1020.

Answer 23

63. a GABA is an amino acid and the major inhibitory neurotransmitter in the CNS. Glycine is also an inhibitory amino acid neurotransmitter and plays a prominent role in the brain and spinal cord. GABA is synthesized from glutamic acid by action of the enzyme glutamic acid decarboxylase. Disorders of this enzyme lead to a deficiency in GABA and subsequently over-activation in the CNS, as is seen in stiff-person syndrome. The GABA_Areceptor is an example of an ionotropic receptor, activation of which leads to opening of chloride channels. The GABA_B receptor is an example of a metabotropic receptor, which is coupled to an inhibitory G protein, inhibiting adenylyl cyclase. Baclofen is an example of a selective GABA_B receptor agonist; benzodiazepines act at GABA_A receptors. Brunton LL, Lazo JS, Parker KL (Eds). Goodman and Gilmans’ Pharmacological Basis of Therapeutics, 11th ed. New York: McGraw-Hill; 2005.

Answer 24

1. e, 2. e, 3. e This patient has relapsing-remitting multiple sclerosis (RRMS). Most patients with this disorder have onset between age 20 and 40, though age of onset ranges from early childhood to late adulthood. Females are affected more than males in a 3:2 ratio. It is more common further north and south of the equator, and more common in Caucasians. RRMS is defined by relapses consistent with demyelination, with or without clinical improvement, but with episodes of clinical stability in between relapses. The term “remitting” is confusing as these patients may not return to clinical normalcy after a relapse. In addition, on MRI, they may have new lesion formation while remaining clinically stable five to ten times as often as they have new clinical episodes. A “relapse” is defined as an episode of new or worsened neurologic symptoms, lasting more than 24 hours, not due to fever or infection. Other synonyms for this are an attack, bout, or exacerbation. The diagnosis is based on two relapses separated in time with clinical evidence of multiple lesions in the central nervous system. The diagnosis can also be made on the basis of multiple lesions on the MRI in combination with an appropriate history and examination, new lesion formation on MRI over time, and new clinical activity over time. A clinically isolated syndrome of demyelination is a single clinical episode consistent with demyelination, but no “second episode” to make a clinical diagnosis of multiple sclerosis. Primary progressive multiple sclerosis usually occurs in older patients. These patients have a gradually progressive course from onset and do not have relapses. They may have a lower burden of MRI lesions than do patients with RRMS. Acute demyelinating encephalomyelitis is an acute disorder, more common in childhood, and often occurring soon after an infection or vaccination. Patients develop a subacute severe disorder with multifocal demyelination in the brain and spinal cord (see discussion to questions 19 to 21). Fulminant multiple sclerosis indicates a rapidly progressive course with repeated relapses that are refractory to standard treatment. There are no laboratory tests that are presently useful in the diagnosis of multiple sclerosis. On occasion, other disorders can mimic multiple sclerosis. Diseases commonly tested for in early evaluation of multiple sclerosis include vitamin B12 deficiency, lupus, Lyme disease in endemic areas, and other inflammatory disorders depending on clinical suspicion. Skin biopsy for small-fiber neuropathy may be useful for patients with paresthesias that affect the limbs and face, that are persistent, and in whom there is no evidence to suggest central demyelination. Brainstem auditory-evoked potentials can be abnormal in the population with multiple sclerosis, but generally are not helpful diagnostically (insensitive in early multiple sclerosis for subclinical brainstem lesions). Somatosensory-evoked, or visual-evoked, potentials may be useful in selected patients to ascertain a second lesion or show slowing, suggestive of central demyelination. CSF may show mild elevation in WBCs, predominantly lymphocytes. Measures of immune activity are sometimes but not always abnormal, including immunoglobulin G synthesis rate and the presence of oligoclonal bands (indicating antibody formation in the spinal fluid compartment). The prognosis for RRMS is better than most people expect. Various studies have shown a good prognosis over 10 years in a representative population without treatment. However, neurologic examination shows abnormalities after 10 years of disease in most patients. The diagnosis of benign multiple sclerosis is a retrospective one after 15 to 20 years of disease without measurable disability. This occurs in approximately 10% to 20% of patients with multiple sclerosis. Fox R, Bethoux F, Goldman MD, et al. Multiple sclerosis: Advances in understanding, diagnosing, and treating the underlying disease. Cleve Clin J Med. 2006; 73:91–102.

Answer 25

4. b, 5. e, 6. c This patient has optic neuritis. The results of a large randomized double-blind treatment trial for acute optic neuritis compared intravenous methylprednisolone with prednisone taper, oral prednisone taper, and placebo. This study showed that recovery was hastened by intravenous methylprednisolone with oral prednisone taper but that visual outcome at 1 year was not significantly affected. Oral steroids were at best no better than placebo, and possibly worse. In about 80% of patients with acute optic neuritis, recovery occurs over weeks. This may be incomplete. Over a 15-year period after an episode of optic neuritis, multiple sclerosis occurs in about 50% of cases. Factors that increase the risk of multiple sclerosis developing include the presence of brain MRI lesions consistent with demyelination and abnormal CSF findings. In the Optic Neuropathy Treatment Trial, patients with visual acuity of 20/50 or better did not measurably benefit from intravenous steroids treatment. Relative afferent pupillary defect is a sign seen in optic neuritis. In this condition, there is involvement of the optic nerve with impaired response to light stimulation. The afferent arm of the pupillary light reflex is affected, in the side of the optic neuritis as compared to the normal eye. This leads to a relative reduction in signal traveling to the Edinger Westphal nucleus in the midbrain from the affected eye. Thus light shone into the affected eye causes a normal consensual light reflex. (Both the pupils constrict.) When the stimulus is shifted to the “good” eye, pupils remain constricted, and then when shifted back to the affected eye, there is relatively less “light,” so the pupils dilate (see also Chapter 1). This is not an indication of an effect on the third nerve, which is the efferent arm of the pupillary light reflex. This does not suggest a particular prognosis. This does not imply a meningeal component. MRI of the brain is ordered primarily to assess evidence and risk of progression to multiple sclerosis. On occasion, imaging of the optic nerve can confirm optic nerve involvement, but it is not critical for the diagnosis of optic neuritis. Rarely, retro-orbital or meningeal processes can cause sudden visual loss, simulating optic neuritis. On occasion, sinus cystic disease can cause impingement on or inflammation in the optic nerve. If there are one or more well-defined demyelinating lesions on MRI, the risk of multiple sclerosis goes from about 20% in 5 years to approximately 80% over 5 years. Multiple treatment trials in patients with a single episode of demyelination and MRI brain lesions have shown benefit from starting medicines that are FDA approved for multiple sclerosis treatment in such patients. In general, when the MRI does not show such lesions, treatment is not indicated beyond steroid therapy acutely. Unless the patient has a history suggestive of syphilis, syphilis serology is not useful. Angiotensin-converting enzyme testing is not useful in this situation unless there are other indications to suggest sarcoidosis. Brainstem auditory-evoked potentials are of low yield in this situation. There is no indication for retinal angiography in typical optic neuritis. It may be useful if there are atypical features such as a horizontal scotoma or very sudden painless onset suggesting a vascular etiology. Balcer LJ. Optic neuritis. N Engl J Med. 2006; 354:1273–1280. Beck RW, Cleary PA, Anderson MM Jr, et al. A randomized, controlled trial of corticosteroids in the treatment of acute optic neuritis. The Optic Neuritis Study Group. N Engl J Med. 1992; 326:581–588.

Answer 26

7. c The patient is having an acute relapse. In this case there is a functional deficit interfering with walking, which is an indication for treatment rather than conservative management. Intravenous methylprednisolone usually given as a dose of 1000 mg daily for 3 to 5 days, with an oral steroid taper, is presently the treatment of choice for acute relapses. Other options include other forms of steroids, different dosing or duration of taper, not using a tapering dose, and high-dose steroids. The goal of treatment is to reduce the functional deficit and increase the speedy recovery of function. The Babinski sign is elicited by stroking the lateral border of the sole of the foot with a moderately sharp object. A normal response is that the great toe goes down (plantar flexion). A positive Babinski sign is when the great toe goes up, often with fanning of the other toes. A full “triple flexion” response is when the ankle dorsiflexes, the knee flexes, and the hip flexes in addition to the Babinski sign. The presence of a Babinski sign implies dysfunction in the corticospinal (pyramidal) tract between the cortex and the lumbar spinal cord. A positive Babinski sign is an indication of an upper motor neuron disorder (corticospinal tract) and not a lower motor neuron disorder (problem affecting the lower motor neuron from the anterior horn of the spinal cord to the neuromuscular junction). Increased exercise during an acute exacerbation has not been shown to be beneficial. However regular exercise in multiple sclerosis has been shown to improve quality-of-life measures and reduce fatigue and depression scales. A crossed adductor sign is seen when performing the patellar reflex. The opposite (crossed) leg adducts (moves medially from the hip). This implies a spread of reflex above the L4 level into L2 and L3 segments of the cord, indicating disinhibition of the reflex arc. This is another upper motor neuron sign. Frohman EM, Shah A, Eggenberger E, et al. Corticosteroids for multiple sclerosis: I. application for treating exacerbations. Neurotherapeutics. 2007; 4(4):618–626.

Answer 27

8. a Multiple sclerosis is more prevalent the further north or south of the equator one lives. The cause for this has not been established. Moving after the age of 12 does not seem to alter this risk. There is no evidence that drinking milk or other dietary measures affect the development of multiple sclerosis. However various epidemiologic studies suggest a link between vitamin D levels and multiple sclerosis, with lower vitamin D levels being correlated with higher risk of multiple sclerosis. Whether this is related to the cause of multiple sclerosis or common factors is unclear. Monozygotic (identical) female twins have a 33% chance of both being affected by multiple sclerosis if one develops multiple sclerosis. This indicates a mixture of genetic and nongenetic factors in the disease causation. Although mononucleosis has been linked to multiple sclerosis at times, the relationship is unclear and no definitive pathogenic relationship can be shown at present. The best evidence against environmental transmission of multiple sclerosis comes from adoption studies that do not show an increase in multiple sclerosis in children adopted into multiple sclerosis-affected families. Multiple sclerosis exacerbations are more likely to occur after infections, but are not related to any specific infection. Motor vehicle accidents and surgical procedures have not been linked to the onset or exacerbation of multiple sclerosis. Fox RJ, Bethoux F, Goldman MD, et al. Advances in understanding, diagnosing and treating the underlying disease. Cleve Clin J Med. 2006; 73:91–102.

Answer 28

9. e Multiple sclerosis is not associated with basophilic or eosinophilic infiltration of the meninges. Lymphocytes enter the CNS from the periphery. There are focal areas of demyelination (plaques) with glial cell infiltration and inflammatory cell accumulation. Macrophages are present in the core of the plaques. Areas of remyelination can be seen (“shadow plaques”). Oligodendroglial cells are reduced in the plaque core and increased at the periphery. Normal-appearing white matter may show loss of axons and some gliosis. Cortical gray matter is affected in multiple sclerosis, but this is poorly visualized with present imaging techniques and is thus under-recorded during life. White matter is typically affected in multiple sclerosis; myelin is removed from around axons, and early in lesion formation, axons are also injured and measurably transected. Lucchinetti CF, Parisi J, Bruck W. The pathology of multiple sclerosis. Neurol Clin. 2006; 23:77–105.

Answer 29

22. c Hypercapnia on arterial blood gas is not a sensitive indicator of the need for intubation in this setting. This patient has a progressive ascending paralysis after a diarrheal illness and albumino-cytologic dissociation evidence from CSF analysis, which is consistent with Guillain Barré syndrome (GBS), an acute inflammatory demyelinating polyneuropathy. Patients with this disorder should be hospitalized and may need intensive unit care, since they may develop respiratory failure, inability to protect the airway, and autonomic dysfunction, with labile blood pressure and cardiac arrhythmias. Therefore, these patients should have close cardiac and ventilatory monitoring with frequent evaluations of negative inspiratory force and vital capacity. Arterial blood gases are not accurate predictors of the need for intubation and mechanical ventilation, since hypoxia and hypercapnia occur late in the course of respiratory failure, once the patient is decompensating. The care of these patients include general supportive care, prevention of complications, rehabilitation, and specific therapies for the inflammatory process, which include plasmapheresis and intravenous immunoglobulin. Steroids play no role in the treatment of GBS. Hughes RA, Wijdicks EF, Barohn R, et al. Practice parameter: Immunotherapy for Guillain-Barre syndrome: Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2003; 61:736–740. Suarez JI. Critical Care Neurology and Neurosurgery, 1st ed. Totowa, NJ: Humana Press; 2004

Answer 30

1. c, 2. c, 3. b The main embryonal layer giving rise to the nervous system is the ectoderm. In early stages of nervous system development, a structure known as the neural plate forms. The notochord, a layer of mesodermal cells in contact with the ectoderm, induces formation of the neural plate from the ectoderm and later signals differentiation of various cell types mediated by inductive signals. The notochord later gives rise to the vertebral column. The neural plate forms a structure known as the neural tube through a process called neurulation. Neurulation involves proliferation and migration of ectodermal cells and invagination, folding, and fusion of the neural plate in a specific pattern. An important step in neurulation includes the formation of a midline groove along which the lateral margins of the neural plate fold. These lateral margins start to fuse in the center, so that for a period of time, there are openings at each end, the anterior and posterior neuropore. Fusion then reaches the neuropores, the anterior one first, then the posterior one, and the neural tube is thus formed. The ventral and dorsal aspects of the neural tube each give rise to specific cell populations and ultimately specific parts of the nervous system. As mentioned, mesodermal cells of the notochord provide signals for differentiation to cells in the ventral aspect of the neural tube. These signals include sonic hedgehog protein and bone morphogenetic proteins, of which several types have been identified. Neurulation occurs at 3 to 6 weeks’ gestation, and failure of crucial processes at any stage leads to a variety of abnormalities, collectively known as neural tube defects. As mentioned earlier, the neural plate undergoes fusion to form the neural tube in different areas at different times, and failure to fuse at each site results in specific defects. Abnormal rostral fusion at the anterior neuropore leads to abnormalities such as encephalocele or anencephaly, whereas abnormal caudal fusion (at the posterior neuropore) leads to disorders such as spina bifida. Following neurulation, the neural tube undergoes segmentation into three vesicles, in a process called specification, whereby different segments begin to acquire cell types and characteristics specific to the CNS structure that will eventually arise from them (malformations resulting from defects in this stage of development are discussed in subsequent questions). The three segments include the prosencephalon, mesencephalon, and rhombencephalon. The prosencephalon subsequently forms the telencephalon, which gives rise to the cerebral hemispheres, as well as the diencephalon, which forms the hypothalamus and thalamus. The rhombencephalon gives rise to the brain stem. Abnormalities during specification, which occurs at 5 to 6 weeks of gestation, lead to disorders such as septo-optic dysplasia (discussed in question 30). As the nervous system becomes more organized and specific areas more specialized, neuronal migration begins along specific routes, and abnormalities of neuronal proliferation and migration in turn lead to specific developmental abnormalities (discussed in subsequent questions). The peripheral nervous system (including the autonomic ganglia) forms from neural crest cells that are derived from the neural tube after it fuses. In addition to peripheral nervous system structures, neural crest cells give rise to the chromaffin tissue of the adrenal medulla and melanocytes. Swaiman KF, Ashwal S, Ferriero DM. Pediatric Neurology Principles and Practice, 4th ed. Philadelphia, PA: Mosby Elsevier; 200

Answer 31

11. e Sacral agenesis is absence of the sacrum, rather than absence of the sacral spinal cord, and is frequently associated with other malformations. The neural tube defects (NTDs) include meningocele, myelomeningocele, diastematomyelia, diplomyelia, and sacral agenesis. Caudal NTDs result from failure of fusion of the posterior neuropore at day 26 of gestation. Meningocele is isolated protrusion of the meninges into a bony defect within the vertebral column. This protrusion is typically covered by skin. It is not usually associated with neurologic deficits, and if neurologic deficit is found, myelomeningocele should be suspected. Myelomeningocele (also known as spinal dysraphism or rachischisis) is protrusion of potentially all layers of intraspinal contents through a bony defect: spinal cord, nerve roots, and meninges. Either the spinal cord may be exposed or a thin membrane may cover the protrusion. They most often occur in the lumbosacral region but can occur at any level. This is a clinically severe NTD associated with hydrocephalus, motor and sensory abnormalities of the legs, and bowel/bladder dysfunction. Myelomeningocele occurs in association with Chiari II malformations (discussed in question 21). Diastematomyelia is splitting of the spinal cord into two portions by a midline septum. Diplomyelia is duplication of the spinal cord and is distinguished from diastematomyelia by the presence of two central canals each surrounded by gray and white matter as in a normal spinal cord. Sacral agenesis, or absence of the whole (or in some cases parts of) the sacrum, classically occurs in association with a variety of other urogenital, gastrointestinal, and spinal cord abnormalities. It has been associated with maternal insulin-dependent diabetes. Autosomal dominant forms associated with homeobox gene mutations have been identified. Clinical manifestations range from mild motor deficits to severe sensory and motor deficits and bowel and bladder dysfunction. Management of NTDs involves surgical approaches and management of complications including hydrocephalus and bowel and bladder dysfunction. A search for associated malformations in other organs (such as the heart or kidneys) should always occur. Bradley WG, Daroff RB, Fenichel GM, et al. Neurology in Clinical Practice, 5th ed. Philadelphia, PA: Elsevier; 2008. Swaiman KF, Ashwal S, Ferriero DM. Pediatric Neurology Principles and Practice, 4th ed. Philadelphia, PA: Mosby Elsevier; 2006.

Answer 32

14. c This patient’s history and examination are consistent with spina bifida occulta. This is a defect in the bony components along the posterior aspect of the vertebral column. It can often be asymptomatic, but an abnormal conus medullaris and filum terminale are possible. The presence of a tuft of hair, implying underlying spina bifida occulta, does not necessarily imply impending cognitive or motor delay. In fact, when early neurologic development is normal, it will typically continue to be so. However, associated neurologic dysfunction may portend future neurologic impairment. When there is associated neurologic dysfunction in a child with a tuft of hair over the lumbar region but with no other evidence of neural tube defect, the disorder is named occult spinal dysraphism. In occult spinal dysraphism, a variety of developmental abnormalities may be seen involving the spinal cord or roots and posterior fossa, and associated findings may include dermoid or epidermoid cysts, intraspinal or cutaneous lipomas, and tethered cord. Diastematomyelia, or splitting of the spinal cord, may also be seen. Rarely, a sinus tract connects the dura with the surface of the skin. In occult spinal dysraphism, neurologic manifestations vary widely and may range from minimal motor deficits and ankle hyporeflexia to bowel and bladder dysfunction, sensory loss, and paraparesis or paraplegia. Although patients may be initially asymptomatic, these neurological deficits can develop suddenly and be irreversible. Swaiman KF, Ashwal S, Ferriero DM. Pediatric Neurology Principles and Practice, 4th ed. Philadelphia, PA: Mosby Elsevier; 2006. Volpe JJ. Neurology of the Newborn, 4th ed. Philadelphia, PA: WB Saunders; 200

Answer 33

16. a Several risk factors for neural tube defects (NTDs) have been identified. NTDs are more common in females. Folate is involved in various pathways of nucleic acid synthesis and DNA methylation reactions, and maternal folate deficiency is a well-established risk factor for NTD. Therefore, prenatal and perinatal maternal supplementation with 0.4 mg folic acid is recommended. Teratogens associated with NTDs include retinoic acid (vitamin A or the acidic form, tretinoin, found in acne medications). Other teratogens associated with NTDs include antiepileptics, particularly valproic acid and carbamazepine, which may lead to NTDs by affecting folate metabolism. Other risk factors for NTDs include maternal diabetes and history of a prior pregnancy resulting in an infant with an NTD. Swaiman KF, Ashwal S, Ferriero DM. Pediatric Neurology Principles and Practice, 4th ed. Philadelphia, PA: Mosby Elsevier; 2006.

Answer 34

19. d Prenatal ultrasonography is used in detecting neural tube defects (NTDs) and characterizing them. Prenatally, in the setting of most NTDs, serum maternal α-fetoprotein level is elevated. α-Fetoprotein is a normal component of fetal CSF, and leakage into the amniotic fluid from an open neural tube leads to elevated amniotic α-fetoprotein level. The extent of elevation correlates with the severity of the NTD. Elevations in amniotic fluid acetylcholinesterase levels also occur, and combined with an elevated α-fetoprotein level, increase sensitivity and specificity in prenatal screening. Ultrasonography also can be used to detect NTDs and characterize them. Prenatal MRI is also used in some cases to assess the extent of the abnormality, aiding in prognostication of neurologic function in life. When an NTD is detected with screening, and/or other abnormalities are detected on ultrasonography, fetal karyotyping to assess for trisomy 13, 18, and others may be done to assist in management of the pregnancy. Swaiman KF, Ashwal S, Ferriero DM. Pediatric Neurology Principles and Practice, 4th ed. Philadelphia, PA: Mosby Elsevier; 2006.

Answer 35

6. d This patient has West Nile virus (WNV) encephalitis, which is an arboviral infection that spreads in the summer months, can occur in epidemics, and is transmitted by mosquitoes of the genus Culex. Most infected patients are asymptomatic, up to 20% may show signs of a febrile viral illness, and less than 1% develop a severe neurologic presentation; elderly patients are particularly at risk for neurologic disease and death. Patients with this neurologic presentation will have manifestations of encephalitis; however, WNV can also invade the anterior horn cells leading to flaccid weakness with areflexia, similar to poliomyelitis. WNV infection may also manifest with cranial neuropathies and tremors. WNV encephalitis is diagnosed by serology and detection of immunoglobulin M (IgM) antibodies in the CSF. CSF PCR is less sensitive, but is diagnostic when positive. MRI is nondiagnostic. Treatment is supportive. This patient does not have findings to support the other conditions listed. Bradley WG, Daroff RB, Fenichel GM, et al. Neurology in Clinical Practice, 5th ed. Philadelphia, PA: Elsevier; 2008.

Answer 36

19. c Tuberculosis can affect the spine, more specifically the vertebral column (Pott’s disease). The most commonly affected region is the midthoracic spine. Patients frequently present with constitutional symptoms, back pain, and muscle spasms, sometimes with findings of compressive radiculopathy or myelopathy. Mycobacterium tuberculosis invades the body of the vertebral column, usually starting in the anterior region of the vertebral bodies, not at the spinous processes. The infectious process tends to disrupt the bone and the intervertebral spaces, leading to vertebral body destruction and collapse, as well as vertebral column deformities with kyphosis and scoliosis. Bradley WG, Daroff RB, Fenichel GM, et al. Neurology in Clinical Practice, 5th ed. Philadelphia, PA: Elsevier; 2008.

Answer 37

10. d Multiple sclerosis is typically an upper motor neuron or CNS disorder and does not cause muscle atrophy. However there are reported cases of some peripheral involvement and muscle atrophy in late multiple sclerosis, but these would be atypical features and suggest other diagnoses. Paresthesias of various types including the above as well as focal areas of pruritus or a sensation of wetness are common in multiple sclerosis. These can occur anywhere on the body. Weakness and gait difficulties are key common symptoms in multiple sclerosis, but do not occur in every patient. Double vision can occur and is usually due to brainstem involvement. Gait or limb ataxia occurs commonly and can be due to cerebellar, cerebellar connection, or sensory tract involvement in multiple sclerosis. Noseworthy JH, Lucchinetti C, Rodriguez M, et al. Multiple sclerosis. N Engl J Med. 2000; 343:938–952.

Answer 38

11. c White cells can be elevated in the CSF in multiple sclerosis. Usually there is a predominance of lymphocytes and no more than 50 cells/mm3. A neutrophilic pleocytosis would be unusual and might suggest another diagnosis. For example this can be seen in Devic’s disease at times (neuromyelitis optica; see discussion to questions 14 to 18). Elevated kappa chains are an indication of antibody formation in the CNS compartment and can be seen in multiple sclerosis. Immunoglobulin G synthesis rate elevation is one measure of increased intrathecal elaboration of antibody and can be seen in multiple sclerosis. Some patients with multiple sclerosis can have normal CSF. The frequency of this finding varies, but a normal CSF does not “rule out” multiple sclerosis. Noseworthy JH, Lucchinetti C, Rodriguez M, et al. Multiple sclerosis. N Engl J Med. 2000; 343:938–952.

SCI - Neurology Flashcards

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