Neurological disorders encompass a wide range of conditions affecting the brain, spinal cord, and peripheral nerves. They are the leading cause of disability globally and the second leading cause of death. This article provides comprehensive coverage of major neurological conditions, their underlying mechanisms, clinical presentations, diagnostic approaches, and therapeutic interventions.
Stroke
| Parameter | Detail |
|---|---|
| Definition | Rapidly developing focal neurologic deficit lasting >24 hours due to vascular cause |
| Classification | Ischemic (87%) vs Hemorrhagic (13%) |
| Global burden | 12.2 million new cases/year, 101 million prevalent cases |
| Risk factors | Hypertension (most important), AFib, diabetes, smoking, hyperlipidemia, obesity, physical inactivity |
Ischemic Stroke Subtypes (TOAST Classification)
| Subtype | Mechanism | Frequency | Key Features |
|---|---|---|---|
| Large artery atherosclerosis | Plaque rupture, artery-to-artery embolism | 25% | >50% stenosis of major cerebral artery; cortical signs |
| Cardioembolic | Embolus from heart (AFib, valvular disease, LV thrombus, PFO) | 25% | Abrupt onset; may affect multiple vascular territories |
| Small vessel (lacunar) | Lipohyalinosis, microatheroma of penetrating arteries | 25% | <15mm infarcts in deep structures (basal ganglia, pons, thalamus, internal capsule); pure motor/sensory syndromes |
| Other determined cause | Dissection, vasculitis, hypercoagulable state, moyamoya | 5% | Younger patients, unusual vascular patterns |
| Cryptogenic | No cause identified despite evaluation | 20% | Often embolic stroke of undetermined source (ESUS) |
Acute Ischemic Stroke Management
| Time Window | Intervention | Details |
|---|---|---|
| Pre-hospital | Activate stroke team, rapid transport | Last known well time critical |
| 0-4.5 hours | IV thrombolysis (alteplase/tenecteplase) | Inclusion: age >=18, measurable deficit, onset time known; Exclusions: recent major surgery, ICH, bleeding diathesis, BP >185/110, glucose <50 or >400 |
| 0-6 hours (anterior circulation) | Mechanical thrombectomy | Large vessel occlusion (ICA, MCA M1/M2); patient selection by CTA/CTP |
| 6-24 hours (extended window) | Mechanical thrombectomy | Selected patients by perfusion imaging (DAWN/DEFUSE-3 criteria) |
| Acute management | BP management, glucose control, O2 if needed | BP: <220/120 (no thrombolysis), <180/105 (post-thrombolysis); maintain normoglycemia |
Hemorrhagic Stroke
| Type | Location | Cause | Treatment |
|---|---|---|---|
| Intracerebral hemorrhage (ICH) | Deep (basal ganglia, thalamus, pons, cerebellum) or lobar | Hypertension (deep), cerebral amyloid angiopathy (lobar), AVMs, anticoagulation, tumors | BP control (SBP <140), reversal of anticoagulation (PCC, vitamin K, protamine), surgical evacuation if cerebellar >3cm or lobar with herniation |
| Subarachnoid hemorrhage (SAH) | Subarachnoid space | Berry aneurysm rupture (85%), perimesencephalic (non-aneurysmal) | Secure aneurysm (coiling or clipping), nimodipine (prevent vasospasm), manage hydrocephalus, vasospasm monitoring (TCD) |
Alzheimer Disease
| Parameter | Detail |
|---|---|
| Definition | Progressive neurodegenerative disorder and most common cause of dementia |
| Prevalence | 55 million worldwide; 10% of population >65 years |
| Pathologic hallmarks | Extracellular beta-amyloid (Abeta) plaques, intracellular neurofibrillary tangles (hyperphosphorylated tau), synaptic loss, neuronal death |
| Genetic forms | Early-onset (<65): APP, PSEN1, PSEN2 mutations (autosomal dominant, <1%); Late-onset: APOE epsilon4 (strongest risk factor) |
Alzheimer Disease Stages
| Stage | Clinical Features | Pathology | Duration |
|---|---|---|---|
| Preclinical | Asymptomatic; biomarker evidence (Abeta PET, CSF Abeta/tau, amyloid PET) | Abeta accumulation begins 15-20 years before symptoms | Years to decades |
| Mild cognitive impairment (MCI) | Cognitive complaints, objective impairment in one domain, preserved function | Abeta plaques + tau tangles in medial temporal lobe | 2-5 years |
| Mild dementia | Memory loss affecting daily life, word-finding, visuospatial deficits | Spread of pathology to temporal, parietal, frontal lobes | 2-4 years |
| Moderate dementia | Significant memory loss, confusion, wandering, behavioral changes, needs assistance | Widespread cortical involvement | 2-5 years |
| Severe dementia | Loss of language, incontinence, complete dependence, immobility | Severe widespread atrophy, neuronal loss | 1-3 years |
Diagnosis of Alzheimer Disease
| Diagnostic Tool | Finding | Utility |
|---|---|---|
| Clinical history | Progressive memory loss, executive dysfunction, visuospatial deficits | Essential (initial assessment) |
| Cognitive testing | MMSE, MoCA, CDR | Quantify impairment |
| MRI brain | Medial temporal lobe atrophy (hippocampal), global cortical atrophy | Rule out other causes (tumors, vascular disease, NPH) |
| FDG-PET | Temporoparietal hypometabolism | Differentiate from FTD (frontotemporal hypometabolism) |
| Amyloid PET | Global cortical amyloid deposition | Confirm Abeta pathology |
| CSF biomarkers | Decreased Abeta42, increased total tau and phospho-tau | Supports diagnosis (early stages) |
| Plasma biomarkers | Abeta42/40 ratio, phospho-tau217 (p-tau217) | Emerging; screening and monitoring |
Alzheimer Disease Treatment
| Drug Class | Examples | Mechanism | Effect |
|---|---|---|---|
| Cholinesterase inhibitors | Donepezil, rivastigmine, galantamine | Increase acetylcholine in synaptic cleft | Symptomatic (modest cognitive benefit); first-line for mild-moderate |
| NMDA receptor antagonist | Memantine | Modulate glutamate excitotoxicity | Symptomatic (modest benefit); moderate-severe stages |
| Anti-amyloid monoclonal antibodies | Aducanumab, lecanemab, donanemab | Remove aggregated amyloid-beta | Disease-modifying (modest slowing of cognitive decline in early disease) |
| Antidepressants | SSRIs (sertraline, citalopram) | Treat comorbid depression | Symptomatic |
| Antipsychotics | Low-dose atypical (risperidone, olanzapine) | Manage agitation, aggression, psychosis | Use cautiously (black box warning in elderly) |
Parkinson Disease
| Parameter | Detail |
|---|---|
| Definition | Progressive neurodegenerative disorder characterized by bradykinesia, rigidity, tremor, and postural instability |
| Prevalence | 1% >60 years; 8-10 million worldwide |
| Pathology | Loss of dopaminergic neurons in substantia nigra pars compacta; Lewy bodies (alpha-synuclein aggregates) |
| Motor symptoms | Bradykinesia (required for diagnosis), resting tremor (4-6 Hz, pill-rolling), rigidity (cogwheel/lead pipe), postural instability (late) |
Parkinson Disease Stages (Hoehn and Yahr)
| Stage | Description |
|---|---|
| 1 | Unilateral involvement only |
| 1.5 | Unilateral plus axial involvement |
| 2 | Bilateral involvement, no balance impairment |
| 2.5 | Mild bilateral disease, recovery on pull test |
| 3 | Mild to moderate bilateral disease, some postural instability, physically independent |
| 4 | Severe disability, still able to walk or stand unassisted |
| 5 | Wheelchair-bound or bedridden unless assisted |
Parkinson Disease Treatment
| Drug Class | Examples | Mechanism | Indication |
|---|---|---|---|
| Levodopa/carbidopa | Sinemet, Rytary | Dopamine precursor (levodopa) with peripheral decarboxylase inhibitor (carbidopa) | First-line; most effective for motor symptoms |
| Dopamine agonists | Pramipexole, ropinirole, rotigotine (patch) | Direct dopamine receptor stimulation | Early-onset; monotherapy or adjunct |
| MAO-B inhibitors | Selegiline, rasagiline, safinamide | Inhibit dopamine breakdown | Early disease, adjunct to levodopa |
| COMT inhibitors | Entacapone, tolcapone, opicapone | Inhibit peripheral levodopa metabolism | Adjunct to levodopa for wearing-off |
| Anticholinergics | Benztropine, trihexyphenidyl | Reduce acetylcholine | Younger patients with prominent tremor |
| Amantadine | Amantadine | Glutamate antagonist, dopamine release | Dyskinesia management |
| Deep brain stimulation (DBS) | — | Electrical stimulation of STN or GPi | Advanced disease with medication-refractory fluctuations/dyskinesia |
Levodopa Complications
| Complication | Description | Management |
|---|---|---|
| Wearing-off | Shortening of levodopa benefit before next dose | Shorten dosing interval, add COMT inhibitor or MAO-B inhibitor |
| Dyskinesias | Involuntary movements (peak-dose, biphasic, off-period) | Reduce individual levodopa doses, add amantadine, DBS |
| On-off fluctuations | Unpredictable switching between ON and OFF states | Optimize dopaminergic therapy, consider DBS |
| Levodopa-resistant symptoms | Freezing of gait, postural instability, falls, speech/swallowing difficulties | Physical therapy, speech therapy, assistive devices; limited pharmacologic options |
| Visual hallucinations | Common in advanced disease | Reduce dopaminergic therapy, add quetiapine or pimavanserin |
Multiple Sclerosis (MS)
| Parameter | Detail |
|---|---|
| Definition | Chronic inflammatory demyelinating disease of the central nervous system |
| Prevalence | 2.8 million worldwide; female:male 3:1 |
| Peak age of onset | 20-40 years |
| Pathology | Focal demyelinating plaques (white matter, cortex, optic nerves, brainstem, spinal cord); perivenular inflammation; axonal loss |
| Etiology | Autoimmune (T-cell mediated); genetic (HLA-DRB1*1501), environmental (EBV, low vitamin D, smoking) |
MS Clinical Course Types
| Type | Description | Frequency |
|---|---|---|
| Relapsing-remitting MS (RRMS) | Well-defined relapses with full or partial recovery; no progression between relapses | 85-90% at onset |
| Secondary progressive MS (SPMS) | Initial RRMS followed by progressive worsening with or without relapses | 50-60% of RRMS within 15-20 years |
| Primary progressive MS (PPMS) | Progressive from onset without relapses | 10-15% |
| Clinically isolated syndrome (CIS) | First episode of demyelination; high risk of MS if MRI shows lesions | — |
| Radiologically isolated syndrome (RIS) | Incidental MRI findings suggestive of MS without symptoms | — |
MS Symptoms
| Domain | Symptoms |
|---|---|
| Motor | Weakness, spasticity, gait impairment, ataxia, tremor |
| Sensory | Numbness, tingling, Lhermitte sign (electric shock with neck flexion), neuropathic pain |
| Visual | Optic neuritis (unilateral, painful eye movement, reduced acuity, afferent pupillary defect), internuclear ophthalmoplegia (INO) |
| Brainstem | Diplopia, vertigo, dysarthria, dysphagia |
| Cerebellar | Intention tremor, dysmetria, ataxic gait |
| Sphincter | Urinary urgency/frequency/incontinence/retention, constipation, erectile dysfunction |
| Cognitive | Processing speed, memory, executive function (frontal/subcortical pattern) |
| Fatigue | >80% of patients; one of the most disabling symptoms |
MS Diagnostic Criteria (McDonald 2017)
| Clinical Presentation | Additional Data Needed |
|---|---|
| 2 or more relapses + objective clinical evidence of 2 or more lesions | None (clinical diagnosis sufficient) |
| 2 or more relapses + objective evidence of 1 lesion (historical) | Dissemination in space demonstrated by MRI or additional clinical relapse |
| 1 relapse + objective evidence of 2 or more lesions | Dissemination in time: new T2 or gadolinium-enhancing lesion on follow-up MRI, or presence of oligoclonal bands in CSF |
| 1 relapse + objective evidence of 1 lesion | Dissemination in space AND time (by MRI or CSF) |
| Progressive course from onset | 1 year progression + 2 of 3: MRI brain (periventricular/cortical/juxtacortical lesions), MRI spinal cord (lesions), CSF (oligoclonal bands) |
MS Disease-Modifying Therapies (DMTs)
| Drug Class | Examples | Efficacy | Route | Key Monitoring |
|---|---|---|---|---|
| Interferon beta | Interferon beta-1a (Avonex, Rebif), Interferon beta-1b (Betaseron, Extavia) | Low-moderate | IM/SC | LFTs, CBC |
| Glatiramer acetate | Copaxone, Glatopa | Low-moderate | SC | Injection site reactions |
| Sphingosine-1-phosphate modulators | Fingolimod, siponimod, ozanimod, ponesimod | High | Oral | Cardiac monitoring (first dose), LFTs, macular edema, lymphopenia |
| Fumarates | Dimethyl fumarate, diroximel fumarate, monomethyl fumarate | Moderate-high | Oral | LFTs, CBC, PML risk (very low) |
| Anti-CD20 (B-cell depleting) | Ocrelizumab, rituximab, ofatumumab | High | IV (ocrelizumab, rituximab) / SC (ofatumumab) | Infusion reactions, infection risk, hepatitis B reactivation |
| Anti-VLA4 (integrin) | Natalizumab | High | IV | PML risk (especially with JC virus + and prior immunosuppression) |
| Anti-CD52 (alemtuzumab) | Alemtuzumab | High | IV | Autoimmune conditions (thyroid, ITP, kidney), infusion reactions |
| Cladribine | Cladribine | High | Oral | Lymphopenia, malignancy risk |
Epilepsy and Seizures
| Term | Definition |
|---|---|
| Seizure | Transient occurrence of signs/symptoms due to abnormal excessive neuronal activity |
| Epilepsy | Two or more unprovoked seizures >24 hours apart, one unprovoked seizure with high recurrence risk, or diagnosis of epilepsy syndrome |
| Status epilepticus | Seizure lasting >5 minutes or multiple seizures without return to baseline; medical emergency |
Seizure Classification (ILAE 2017)
| Seizure Type | Subtypes | Features |
|---|---|---|
| Focal onset (aware/impaired awareness) | Motor onset: automatisms, atonic, clonic, epileptic spasms, hyperkinetic, myoclonic, tonic | Originates in one hemisphere; may spread (secondary generalization) |
| Focal onset (non-motor) | Autonomic, behavior arrest, cognitive, emotional, sensory | |
| Generalized onset (motor) | Tonic-clonic, clonic, tonic, myoclonic, myoclonic-tonic-clonic, myoclonic-atonic, atonic, epileptic spasms | Involves both hemispheres from onset |
| Generalized onset (non-motor) | Typical absence, atypical absence, myoclonic absence, eyelid myoclonia | |
| Unknown onset | Motor, non-motor, unclassified |
Common Epilepsy Syndromes
| Syndrome | Age of Onset | Seizure Types | Prognosis |
|---|---|---|---|
| Childhood absence epilepsy | 4-10 years | Typical absence | Excellent (remission by adolescence) |
| Juvenile myoclonic epilepsy | 12-18 years | Myoclonic (especially morning), GTC, absence | Good (lifelong treatment usually needed) |
| Benign childhood epilepsy with centrotemporal spikes (BECTS) | 3-13 years | Focal (nocturnal orofacial, drooling) | Excellent (remission by adolescence) |
| Lennox-Gastaut syndrome | 1-8 years | Multiple types (tonic, atonic, atypical absence), developmental delay | Poor (intractable seizures) |
| West syndrome (infantile spasms) | 3-12 months | Epileptic spasms, hypsarrhythmia on EEG | Variable (developmental outcomes poor) |
| Temporal lobe epilepsy | Any age (peak 10-30) | Focal impaired awareness (automatisms, déjà vu, rising epigastric sensation) | Variable (may be refractory, good surgical outcomes) |
Antiseizure Medications (ASMs)
| Drug | Mechanism | Seizure Types | Key Side Effects |
|---|---|---|---|
| Levetiracetam | SV2A binding | Focal, generalized | Irritability, dizziness, somnolence |
| Lamotrigine | Sodium channel blockade | Focal, generalized (including absence) | Rash (SJS/TEN risk - slow titration), dizziness, diplopia |
| Valproate | Multiple mechanisms (GABA, sodium channels) | Generalized, absence, myoclonic | Weight gain, tremor, hepatotoxicity, teratogenicity, PCOS |
| Phenytoin | Sodium channel blockade | Focal, generalized (GTC) | Gingival hyperplasia, nystagmus, ataxia, osteoporosis, drug interactions |
| Carbamazepine | Sodium channel blockade | Focal, generalized (GTC) | Hyponatremia, rash, Stevens-Johnson syndrome (Asian: HLA-B*1502), dizziness, drug interactions |
| Oxcarbazepine | Sodium channel blockade | Focal | Hyponatremia, dizziness, rash |
| Topiramate | Multiple mechanisms (GABA, glutamate, carbonic anhydrase) | Focal, generalized | Weight loss, word-finding difficulty, kidney stones, glaucoma |
| Zonisamide | Sodium/calcium channel | Focal, generalized | Weight loss, somnolence, kidney stones |
| Lacosamide | Slow sodium channel inactivation | Focal | PR prolongation, dizziness, diplopia |
| Perampanel | AMPA glutamate receptor antagonist | Focal, generalized (GTC) | Irritability, falls, dizziness, weight gain |
| Brivaracetam | SV2A binding | Focal | Irritability, dizziness (less than levetiracetam) |
| Clobazam | Benzodiazepine (GABA-A) | Lennox-Gastaut, adjunctive | Tolerance, sedation |
| Ethosuximide | T-type calcium channel | Absence seizures | GI upset, headache, bone marrow suppression |
Migraine
| Parameter | Detail |
|---|---|
| Definition | Recurrent headache disorder with moderate to severe unilateral pulsating pain, lasting 4-72 hours |
| Prevalence | 15% globally; 20% of women, 10% of men |
| Phases | Prodrome (hours to days), aura (minutes to 1 hour), headache (4-72 hours), postdrome (hours to days) |
| Migraine with aura | 25% of migraineurs; visual (scotoma, fortification spectra), sensory (numbness/tingling), speech disturbance |
| Triggers | Stress, hormonal changes (menses), sleep deprivation, skipped meals, weather changes, alcohol, certain foods |
Migraine Treatment
| Category | Drugs | Notes |
|---|---|---|
| Acute (mild-moderate) | NSAIDs (ibuprofen, naproxen, diclofenac), acetaminophen, combination analgesics | First-line for mild attacks |
| Acute (moderate-severe) | Triptans: sumatriptan, rizatriptan, eletriptan, zolmitriptan, naratriptan, frovatriptan | 5-HT1B/1D agonists; avoid in CAD, uncontrolled HTN, hemiplegic migraine |
| Acute (alternative) | Gepants: ubrogepant, rimegepant (CGRP antagonists) | No vasoconstriction; for patients with triptan contraindications |
| Acute (alternative) | Lasmiditan (5-HT1F agonist) | No vasoconstriction; dizziness and fatigue common |
| Acute (severe/status) | Dihydroergotamine (DHE), antiemetics (metoclopramide, prochlorperazine), ketorolac | IV/IM for emergency department |
| Preventive (mild-moderate) | Beta-blockers (propranolol, metoprolol), amitriptyline, topiramate, valproate | First-line oral preventives |
| Preventive (injectable) | CGRP mAbs: erenumab, galcanezumab, fremanezumab, eptinezumab | Monthly or quarterly injections |
| Preventive (botulinum toxin) | OnabotulinumtoxinA | 31 injections every 12 weeks; for chronic migraine (>=15 days/month) |
Peripheral Neuropathy
| Type | Location | Most Common Causes | Symptoms |
|---|---|---|---|
| Mononeuropathy | Single nerve | Carpal tunnel (median), ulnar neuropathy, peroneal neuropathy, Bell palsy (facial nerve) | Pain, weakness, sensory loss in specific nerve distribution |
| Polyneuropathy | Multiple nerves (distal, symmetric) | Diabetes (most common), alcohol, chemotherapy, B12 deficiency, HIV, CKDis, paraproteinemia, hereditary (CMT) | Length-dependent: numbness, tingling, burning in feet, then hands (stocking-glove), weakness, gait instability |
| Mononeuritis multiplex | Multiple individual nerves | Vasculitis (PAN, SLE, RA), sarcoidosis, diabetes, leprosy | Asymmetric, stepwise involvement of multiple nerves |
| Polyradiculopathy | Nerve roots | Guillain-Barre (acute), CIDP (chronic), diabetes, CMV, Lyme | Symmetric, proximal and distal weakness, areflexia, sensory loss |
Amyotrophic Lateral Sclerosis (ALS)
| Parameter | Detail |
|---|---|
| Definition | Progressive neurodegenerative disease affecting upper and lower motor neurons |
| Prevalence | 5-10 per 100,000 |
| Age of onset | Average 55-65 years |
| Pathology | TDP-43 aggregates, SOD1 mutations (familial), C9orf72 repeat expansion, neuronal loss in motor cortex, brainstem, spinal cord |
| Prognosis | Median survival 2-5 years from onset |
ALS Clinical Features
| Motor Neuron Type | Signs |
|---|---|
| Upper motor neuron (UMN) | Spasticity, hyperreflexia, clonus, Babinski sign, pseudobulbar affect (emotional lability) |
| Lower motor neuron (LMN) | Muscle weakness, atrophy, fasciculations, cramps, hyporeflexia, flaccidity |
ALS Patterns of Onset
| Onset Type | Initial Symptoms | Frequency |
|---|---|---|
| Limb onset | Focal weakness (foot drop, hand weakness), muscle atrophy, fasciculations | 70% |
| Bulbar onset | Dysarthria (slurred speech), dysphagia, sialorrhea | 25% |
| Respiratory onset | Dyspnea, orthopnea | 5% |
ALS Treatment
| Intervention | Effect |
|---|---|
| Riluzole | Glutamate antagonist; extends survival by 2-3 months |
| Edaravone | Free radical scavenger; slows functional decline in selected patients |
| NIPPV (non-invasive positive pressure ventilation) | Improves survival and quality of life in respiratory involvement |
| PEG (percutaneous endoscopic gastrostomy) | Nutritional support for dysphagia |
| Symptomatic management | Sialorrhea (glycopyrrolate, botulinum toxin), spasticity (baclofen, tizanidine), sialorrhea, pain, depression, insomnia |
| Multidisciplinary care | Neurology, pulmonology, nutrition, speech therapy, physical therapy, social work |