Neurological disorders affect the brain, spinal cord, peripheral nerves, and neuromuscular junction. They are the leading cause of disability worldwide and the second leading cause of death. Stroke alone accounts for over 6 million deaths annually. Advances in neuroimaging, molecular genetics, and neuroimmunology have transformed the diagnosis and treatment of these conditions.
Cerebrovascular Disease
Ischemic Stroke
Ischemic stroke accounts for 87% of all strokes and results from obstruction of a cerebral artery. Etiology includes large artery atherosclerosis, cardioembolism (atrial fibrillation, valvular disease), small vessel disease (lacunar infarcts), and cryptogenic causes. The core of the infarct undergoes irreversible injury, while the surrounding penumbra — tissue at risk but not yet infarcted — is the target of acute intervention.
Clinical presentation. Sudden onset of focal neurological deficits corresponding to the affected vascular territory: weakness, sensory loss, aphasia (dominant hemisphere), neglect (non-dominant hemisphere), visual field deficits, ataxia, and dysarthria. The FAST mnemonic (Facial droop, Arm drift, Speech difficulty, Time) aids public recognition.
Acute management. Intravenous thrombolysis with alteplase within 4.5 hours of symptom onset improves outcomes. Endovascular thrombectomy for large vessel occlusion extends the window to 24 hours in selected patients based on perfusion imaging. Rapid reperfusion is the strongest determinant of favorable outcome.
Secondary prevention. Antiplatelet therapy, statins, blood pressure control, smoking cessation, diabetes management, anticoagulation for cardioembolic sources (e.g., atrial fibrillation), and carotid endarterectomy or stenting for significant carotid stenosis.
Hemorrhagic Stroke
Intracerebral hemorrhage (ICH) is bleeding into the brain parenchyma, most commonly from hypertensive microangiopathy or cerebral amyloid angiopathy. Subarachnoid hemorrhage (SAH) is bleeding into the subarachnoid space, typically from a ruptured saccular aneurysm. Management focuses on blood pressure control, reversal of anticoagulation, surgical evacuation (for cerebellar or lobar ICH), aneurysm clipping or coiling (for SAH), and management of complications (hydrocephalus, vasospasm, seizures).
Epilepsy
Epilepsy is a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures. A seizure is a transient occurrence of signs or symptoms due to abnormal excessive or synchronous neuronal activity. Epilepsy is diagnosed after two unprovoked seizures or one unprovoked seizure with a high risk of recurrence.
Classification. Seizures are classified as focal (originating in one hemisphere) or generalized (involving both hemispheres simultaneously). Focal seizures may be aware or impaired awareness; motor or non-motor onset. Generalized seizures include tonic-clonic, absence, myoclonic, clonic, tonic, and atonic types.
Etiology. Genetic (channelopathies, metabolic disorders), structural (trauma, stroke, tumor, malformations of cortical development), infectious (meningitis, encephalitis, neurocysticercosis), metabolic, immune, and unknown causes.
Treatment. First-line treatment is antiseizure medication (ASM) selected based on seizure type and epilepsy syndrome. Approximately 70% of patients achieve seizure freedom with appropriate ASM. For drug-resistant epilepsy (failure of two tolerated ASM trials), epilepsy surgery evaluation should be considered. Surgical resection of the epileptic focus offers a 60–80% chance of seizure freedom in appropriately selected patients. Vagus nerve stimulation and responsive neurostimulation are options for non-surgical candidates.
Neurodegenerative Diseases
Alzheimer Disease
Alzheimer disease is the most common cause of dementia, accounting for 60–80% of cases. It is characterized by progressive cognitive decline, primarily affecting memory, language, and executive function. Neuropathology shows extracellular amyloid-beta plaques and intracellular neurofibrillary tangles composed of hyperphosphorylated tau.
Pathophysiology. The amyloid cascade hypothesis proposes that accumulation of amyloid-beta oligomers triggers tau pathology, synaptic dysfunction, and neuronal loss. Genetic risk factors include APOE ε4 (the strongest genetic risk factor for late-onset AD), while autosomal dominant mutations in APP, PSEN1, and PSEN2 cause early-onset familial AD.
Diagnosis. Clinical diagnosis is based on history, cognitive testing (MoCA, MMSE), and exclusion of other causes. Biomarker testing (CSF amyloid-beta and tau, amyloid PET, tau PET) improves diagnostic accuracy and enables preclinical detection.
Treatment. Cholinesterase inhibitors (donepezil, rivastigmine, galantamine) and the NMDA receptor antagonist memantine provide modest symptomatic benefit. Lecanemab and donanemab, anti-amyloid monoclonal antibodies, slow cognitive decline by approximately 30% in early Alzheimer disease. No disease-modifying therapy has yet demonstrated efficacy in advanced stages.
Parkinson Disease
Parkinson disease is a progressive movement disorder caused by loss of dopaminergic neurons in the substantia nigra pars compacta. Lewy bodies (aggregates of alpha-synuclein) are the pathological hallmark.
Clinical features. Motor manifestations include resting tremor, bradykinesia, rigidity, and postural instability. Non-motor symptoms — hyposmia, REM sleep behavior disorder, constipation, depression, anxiety, and cognitive impairment — often precede motor symptoms by years.
Treatment. Levodopa remains the most effective symptomatic therapy. Dopamine agonists, MAO-B inhibitors, and amantadine are alternatives. Deep brain stimulation of the subthalamic nucleus or globus pallidus interna is effective for motor fluctuations and dyskinesia. Physical, occupational, and speech therapy improve function and quality of life.
Multiple Sclerosis
Multiple sclerosis is an immune-mediated demyelinating disease of the central nervous system. It typically presents in young adults with relapsing-remitting episodes of neurological dysfunction (optic neuritis, transverse myelitis, brainstem syndromes). Over time, most patients develop secondary progressive MS with accumulating disability independent of relapses.
Diagnosis. The McDonald criteria integrate clinical presentation, MRI findings (demyelinating lesions in space and time), and CSF analysis (oligoclonal bands).
Treatment. Disease-modifying therapies for relapsing MS include interferons, glatiramer acetate, dimethyl fumarate, teriflunomide, fingolimod, natalizumab, ocrelizumab, and cladribine. Ocrelizumab is also approved for primary progressive MS. Acute relapses are treated with high-dose corticosteroids.
Neuromuscular Disorders
Amyotrophic lateral sclerosis (ALS). A progressive neurodegenerative disease affecting upper and lower motor neurons. Mean survival is 3–5 years. Riluzole and edaravone modestly slow progression. Multidisciplinary care, non-invasive ventilation, and nutritional support improve survival and quality of life.
Myasthenia gravis. An autoimmune disorder of the neuromuscular junction caused by antibodies against the acetylcholine receptor (or MuSK). Fluctuating muscle weakness affects the eyes, bulbar muscles, and limbs. Treatment includes acetylcholinesterase inhibitors, immunosuppression (corticosteroids, mycophenolate), thymectomy (for thymoma), and complement inhibitors (eculizumab).
Peripheral neuropathy. A heterogeneous group of disorders affecting peripheral nerves. Causes include diabetes, vitamin B12 deficiency, uremia, alcohol, chemotherapy, autoimmune disease (Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy), and inherited conditions (Charcot-Marie-Tooth disease). Treatment addresses the underlying cause and provides symptomatic relief (gabapentin, tricyclic antidepressants, pregabalin).
Summary
Neurological disorders encompass a vast range of pathologies affecting every level of the nervous system. Acute interventions for stroke and seizures can prevent or reduce permanent disability. Neurodegenerative diseases, though not yet curable, are increasingly amenable to symptomatic treatment and, in the case of Alzheimer disease, disease modification through anti-amyloid therapy. The convergence of neuroimaging, genetics, and immunology continues to reveal new therapeutic targets and improve outcomes for patients with neurological disorders.