START FROM THE BOOK AND DIRTY MEDICINE AND TABLES IN THE NOTS
WE WILL START WITH PATHO
Amyotrophic lateral sclerosis ALS
Amyotrophic lateral sclerosis causes degeneration of both upper and lower motor neurons and can result in bulbar and skeletal muscle weakness AND ATROPHY .
Denervation atrophy can affect the diaphragm and contribute to respiratory failure. MOST COMMON CAUSE OF DEAT IN ALS
decreased vital capacity, ineffective cough,chronic aspiration.
Loss of upper motor neurons leads to atrophy of the precentral motor gyrus and degeneration of the corticospinal tracts. Loss of lower motor neurons leads to thinning of the anterior roots of the spinal cord and atrophy of cranial nerve motor nuclei.
🧠 Subarachnoid Hemorrhage (SAH)
Cause:
Usually due to rupture of a saccular (berry) aneurysm.
Classic Presentation:
“Thunderclap” headache (sudden, severe).
± Confusion, loss of consciousness, meningismus (neck stiffness).
Diagnosis:
Noncontrast CT scan → blood in subarachnoid space (between arachnoid & pia mater).
Major Complications (Days–Weeks Later): IMPORTANT
Rebleeding
Hydrocephalus
Seizures
Arterial vasospasm → most common cause of delayed neurological decline (3–12 days after SAH)
Mechanism of Vasospasm:
Damaged RBCs release vasoconstrictive factors.
Endothelial injury ↓ NO (vasodilator) → unopposed vasoconstriction → delayed cerebral ischemia.
CT often normal despite ischemia. UNLIKE REBLEEDING
Prevention/Treatment:
Nimodipine (selective Ca²⁺ channel blocker):
Parkinson disease
caused by dopaminergic neurodegeneration.
Traumatic brain injuries can accelerate neurodegeneration, leading to a higher incidence and earlier onset of Parkinson disease.
The most effective surgical targets are the STN (reduces excess GPi excitation) and the GPi (reduces excess thalamic inhibition); inhibition of either nucleus has been shown to improve motor fluctuations and dyskinesia seen with advanced PD.
Paraneoplastic syndromes
Paraneoplastic syndromes can occur due to the production of hormone-like substances from tumor cells.
They can also result from immune reactions against tumor cells that cross-react with normal cells, causing dysfunction and/or damage to healthy organs and tissues.
Neurologic paraneoplastic syndromes (eg, paraneoplastic cerebellar degeneration) are an autoimmune phenomenon.(cross-reacts with Purkinje neuron antigens)
Patients exhibit progressively worsening dizziness, limb and truncal ataxia, dysarthria, and visual disturbances (eg, diplopia, oscillopsia)
Diabetic neuropathy
WHO IT HAPPENS ? hyalinization of endoneurial arteries and ischemic nerve damage. In addition, accumulation of toxic substances within neurons results in deranged metabolism and increased oxidative stress. IMPORTANT
Diabetes mellitus is the most common cause of peripheral polyneuropathy in adults. Common findings include numbness and paresthesias in a stocking-glove distribution and decreased proprioception due to degeneration of large-fiber sensory axons.
Small-fiber injury is characterized by predominance of positive symptoms (eg, pain, paresthesias, allodynia).
IMPORTANT Large-fiber involvement is characterized by predominance of negative symptoms (eg, numbness, loss of proprioception and vibration sense, sensory ataxia [eg, positive Romberg sign], diminished ankle reflexes).
IMPORTANT (MONO) ISCHEMIC CAUSE
Diabetic CN III mononeuropathy classically presents with acute onset diplopia.
On examination, the affected eye assumes a “down and out” position
Ptosis also occurs due to paralysis of the levator palpebrae.
spares peripheral parasympathetic fibers SO, normal light and accommodation reflexes.
Alzheimer disease
Alzheimer disease is characterized by decreased levels of acetylcholine in the nucleus basalis of Meynert and the hippocampus, caused by diminished activity of choline acetyltransferase.
Atrophy is most pronounced in the temporoparietal lobes and hippocampus IMPORTANT. Hippocampal atrophy is evident even in the early stages of the disease and can be detected by brain MRI.
associated with beta-amyloid deposits in the brain parenchyma (neuritic plaques) and walls of cerebral vessels (amyloid angiopathy).
Amyloid is an abnormally folded (insoluble) extracellular protein that has apple-green birefringence when stained with Congo red and viewed under polarized light.IMPORTANT
Wilson disease
It typically presents in young adults with liver disease, neuropsychiatric symptoms (eg, gait disturbance, dysarthria, depression, personality changes),
and Kayser-Fleischer rings on slit lamp examination.
IMPORTANT
Carpal tunnel syndrome (CTS)
Carpal tunnel syndrome (CTS) is a peripheral mononeuropathy caused by compression of the median nerve in the carpal tunnel, an area between the carpal bones and transverse carpal ligament on the palmar surface of the wrist.
CTS is associated with conditions that reduce carpal tunnel space, including pregnancy (fluid accumulation), hypothyroidism (glycosaminoglycan buildup), diabetes mellitus (connective tissue thickening), and rheumatoid arthritis (tendon inflammation). Patients with a long history of hemodialysis can develop median nerve compression through deposition of beta-2 microglobulin (dialysis-associated amyloidosis) in the carpal tunnel.
IMPORTANT:
Symptoms and signs of CTS often occur bilaterally (in up to 65% of patients) and include:
sensory impairment, pain, and/or paresthesias in the median nerve distribution (palmar surface of the first 3 digits and radial half of the fourth). Symptoms are usually worse at night.
motor weakness during thumb abduction/opposition and thenar atrophy.
Tinel sign (tapping over the flexor surface of the wrist reproduces symptoms) and Phalen sign (flexion of the wrist reproduces symptoms).
dementia
It manifests initially with changes in personality, social behavior, and language that progress over time to a more global dementia with obvious neurocognitive deficits.
It is associated with neurofibrillary tangles due to abnormal tau proteins (also seen in Alzheimer dementia) and pathologically ubiquitinated TDP-43 (also seen in amyotrophic lateral sclerosis). IMPORTANT
1.Creutzfeldt-Jakob disease is a prion disease characterized by rapidly progressive dementia, myoclonus, and death within a year of symptom onset. VERY TYPICAL PRESENTATION
It is caused by the accumulation of an abnormally folded (ie, beta pleated sheet) protein that is resistant to proteases IMPORTANTT and can trigger similar conformational changes in other normally folded proteins.
2.HIV-associated dementia should be suspected in patients with AIDS who have progressive cognitive decline. The characteristic histopathologic finding is microglial nodules (groups of activated microglia/macrophages around small areas of necrosis) and multinucleated giant cells. IMPORTANT
Ischemia and/or infarcts due to:
Large-vessel atherosclerosis
Small-vessel disease (eg, arteriolosclerosis)
Cerebral amyloid angiopathy
Clinical manifestations
Early, prominent executive dysfunction
Subtypes:
Multi-infarct: often with stepwise decline
Strategic infarct: associated with localizing cortical deficits
Subcortical vascular encephalopathy: associated with subcortical signs (eg, urinary incontinence, gait disturbances)
Imaging findings
Cortical infarcts
Subcortical lacunar infarcts
White matter hyperintensities
Cerebral palsy CP
Cerebral palsy is a nonprogressive neurologic injury that most commonly presents with delayed gross motor milestones, spasticity, and hyperreflexia.
Premature infants are particularly susceptible due to periventricular leukomalacia (white matter necrosis).IMPORTANT
Cavernous hemangiomas
Cavernous hemangiomas are vascular malformations composed of abnormally dilated capillaries separated by thin connective tissue septa.
The lack of structural support gives them a tendency to bleed, and those that occur in the brain can present with neurologic deficits and seizures
increased risk of intracerebral hemorrhage and seizure IMPORTANTT
Tabes dorsalis
Most patients with tertiary syphilis will have a positive VDRL and mild lymphocytic pleocytosis on CSF analysis
Tabes dorsalis, a late form of neurosyphilis( years or decades after initial infection with Treponema pallidum), causes progressive degeneration of the dorsal columns and dorsal roots of the spinal cord.
Manifestations include loss of proprioception and vibratory sensation, severe lancinating pains( Sharp, stabbing pains), and sensory ataxia (eg, wide-based gait, positive Romberg sign).
Many patients also have Argyll Robertson pupils.
This finding is marked by small, irregularly shaped pupils that fail to constrict to light but that constrict normally to accommodation (light-near dissociation).
Neuroblastoma
Pathogenesis
Neural crest origin
Involves adrenal medulla, sympathetic chain
Clinical features
Median age <2
Abdominal mass
Periorbital ecchymoses (orbital metastases)
Spinal cord compression from epidural invasion (“dumbbell tumor”)
Opsoclonus-myoclonus syndrome\
Diagnostic findings
Elevated catecholamine metabolites
Small, round blue cells on histology
N-myc gene amplification
lacunar infarct.
a small cavitary lesion in the internal capsule, characteristic of a lacunar infarct.
SLIT LIKE WHITE MATTER CAVITIES WITH SURRONDING GLIOSIS
This type of stroke affects the small penetrating arterioles that supply the deep brain structures (eg, basal ganglia, pons) and subcortical white matter (eg, internal capsule, corona radiata).
Lacunar infarcts are primarily associated with chronic hypertension, which promotes lipohyalinosis, microatheroma formation, and hardening/thickening of the vessel wall (hypertensive arteriolar sclerosis). IMPORTANT
This leads to progressive narrowing of the arteriolar lumen and predisposes to thrombotic vessel occlusion, which causes characteristic clinical syndromes, depending on the portion of the brain affected:
1)Posterior limb of the internal capsule and/or basal pons - pure motor hemiparesis or ataxia-hemiplegia syndrome (ie, ipsilateral limb ataxia out of proportion to motor deficit)
2)Genu/anterior limb of the internal capsule and/or basal pons - dysarthria-clumsy hand syndrome (ie, dysarthria and dysphagia with clumsiness of one hand)
3)Ventroposterolateral or ventroposteromedial thalamus - pure sensory stroke
In the acute setting, CT imaging may not reveal the expected hypodensity of ischemic stroke due to the small infarct size (usually <15 mm).
After several weeks, these necrotic lesions turn into cavitary spaces filled with cerebrospinal fluid and surrounded by scar tissue called lacunas.IMPORTANT
axillary lymph node dissection
Multiple nerves are at risk for injury during axillary lymph node dissection.
Intercostobrachial nerve injury results in sensory dysfunction (eg, burning, numbness) to the skin of the axilla and medial upper arm. IMPORTANT
Injury to the long thoracic (serratus anterior), thoracodorsal (latissimus dorsi), medial pectoral (pectoralis minor and major), or lateral pectoral (pectoralis major) nerves results in motor deficits to corresponding muscles.
LEG NERVES INJURY
1)The common fibular nerve is superficially located at the proximal fibula, leaving it vulnerable to injury by compression by the fibular head (eg, prolonged lying on the affected side). Patients typically have weakness of foot dorsiflexion (ie, footdrop), foot eversion, and toe extension, along with sensory loss over the lateral lower leg and dorsal foot.
2) the femoral nerve is rarely affected during hip replacement, this injury would result in weakness on hip flexion and knee extension, along with sensory loss over the anterior thigh.
3)The lateral sural cutaneous nerve is a branch of the common fibular nerve that provides sensory innervation to the posterolateral lower leg; it does not provide motor innervation.
4)sciatic nerve injury is trauma or surgery involving the hip joint. However, sciatic nerve injury causes deficits in the common fibular, tibial, and sural nerve distributions, with loss of sensation over the posterior leg and weakness involving the hamstrings and most of the muscles of the lower leg.
5)The tibial nerve can be injured at the knee by trauma or compression (eg, Baker cyst in the popliteal fossa). Proximal tibial neuropathy usually causes weakness of foot plantar flexion and decreased sensation over the sole.
Crossed signs
Crossed signs (ie, ipsilateral cranial nerve dysfunction with contralateral limb weakness) are typical of a brainstem stroke.
A stroke in the medial medulla often results in contralateral limb weakness with ipsilateral tongue weakness, which causes tongue deviation to the weak side.CN12
LATERAL medulla
MEDIAL PONS
LATERAL PONS
MIDBRAIN
Guillain-Barré syndrome
Guillain-Barré syndrome is an acute demyelinating polyneuropathy.
It is thought to be due to molecular mimicry and is commonly preceded by an upper respiratory viral illness or gastroenteritis.
Segmental demyelination of the peripheral nerves and an endoneural inflammatory infiltrate are seen on light microscopy. IMPORTANT
Multiple Sclerosis (MS) & Conduction Block
Key Clinical Clues:
Internuclear ophthalmoplegia (INO): impaired adduction of one eye with lateral gaze
History of optic neuritis: transient blurred vision + eye pain with movement
Sodium channels concentrated only at these nodes → fast transmission (>10× faster)
Myelin loss → distance between sodium channels too great → conduction block
LOSS saltatory conduction (Action potential “jumps” between nodes of Ranvier)
and macrophages are seen surrounding oligodendrocytes and myelin sheaths.
Oligoclonal bands are highly sensitive but nonspecific in patients with MS.
Wernicke encephalopathy
Wernicke encephalopathy
Risk factors
Chronic alcohol use (most common)
Malnutrition (eg, anorexia, gastric bypass surgery)
Pathophysiology
Thiamine deficiency → impaired glucose metabolism & ATP production → neuronal injury/death (eg, mammillary bodies)
May be precipitated by high metabolic demand or high glucose load
Clinical findings VERY IMPORTANT
Encephalopathy
Oculomotor dysfunction
Ataxia
Management AND prognosis
Thiamine infusion reverses most symptoms.
Memory impairment may be chronic/irreversible (Korsakoff syndrome).
Neoplastic spinal cord compression METZ
Neoplastic spinal cord compression most commonly results from local extension of vertebral metastases into the epidural space.
Presenting symptoms typically include severe back pain (often worse at night), motor weakness, and/or sensory deficits. Urinary and fecal retention or incontinence are common late-stage findings.
Delirium (Medication-Induced)
Definition:
Acute disturbance in attention, awareness, and cognition that develops over hours to days and fluctuates throughout the day.
Key Features:
VERY IMPORTANTTT
Acute onset and fluctuating course
Altered mental status: impaired consciousness, disorientation, hallucinations
Reversible once the cause is treated
Common Causes:
Multifactorial, often due to:
Acute medical illness
Drug intoxication/withdrawal
Medication side effects (especially psychoactive drugs)
High-Risk Drugs:
Anticholinergics
Antihistamines ALLERGY
Benzodiazepines
Sedative-hypnotics
Opioids
Treatment:
Identify and remove the offending agent or treat the underlying cause
Provide supportive care and environmental reorientation
Huntington disease
AD
neurodegenerative disease that leads to the accumulation of abnormal, toxic huntingtin protein in neural cells.
HTT GENE CHROMOSOME 4
LOW GABA ,LOW ACH ,HIGH DOPAMINE
Inhibitory GABAergic neurons in the caudate nuclei are most susceptible, and their loss is responsible for the characteristic manifestations of Huntington disease (eg, chorea, behavioral abnormalities).
ENLARGE OF FRONTAL HORN OF LATERAL VENTRICLE
