MSC Neuro 25 p2

Idiopathic (Primary) Parkinson's Disease: Progressive neurodegenerative disorder mainly affecting dopaminergic neurons in the substantia nigra pars compacta (SNpc), leading to dopamine deficiency.

Secondary Parkinsonism: Caused by known factors such as:

Vascular lesions (stroke)

Drug-induced (neuroleptics, metoclopramide)

Toxic exposures (manganese, carbon monoxide)

Post-traumatic, infectious (encephalitis)

Tumors or mass effect on basal ganglia

Parkinson Plus Syndromes: Progressive supranuclear palsy, multiple system atrophy, corticobasal degeneration, Lewy body dementia, etc.

Genetics: Familial cases (~10-15%), with multiple gene mutations implicated (SNCA, LRRK2, PINK1, Parkin).

Environmental: Pesticides, herbicides, industrial toxins, head trauma implicated in pathogenesis.

Pathogenesis

Dopamine Deficiency: Loss of pigmented dopaminergic neurons in SNpc leads to decreased dopamine in basal ganglia circuits.

Alpha-synucleinAggregation: Misfolded alpha-synuclein forms Lewy bodies, toxic oligomers propagating neurodegeneration.

Mitochondrial Dysfunction: Impaired complex I of respiratory chain, increased oxidative stress.

Neuroinflammation: Activation of microglia and astrocytes contributes to neurodegeneration.

Impaired Protein Clearance: Dysfunctional autophagy and proteasome pathways lead to accumulation of toxic proteins.

Clinical Features

Motor Symptoms (Cardinal signs):

Rest tremor (pill-rolling, 4-6 Hz)

Bradykinesia (slowness and poverty of movement)

Symptomatic therapy:

Levodopa (+carbidopa) — gold standard for symptom control.

Dopamine agonists (pramipexole, ropinirole).

MAO-B inhibitors (selegiline), COMT inhibitors.

Anticholinergics for tremor.

Amantadine for dyskinesias.

Neuroprotection: Ongoing research; no definitive therapy yet.

Surgical treatment:

Deep brain stimulation (DBS) of subthalamic nucleus or globus pallidus interna.

Pallidotomy or thalamotomy in selected cases.

Experimental cell transplantation under investigation.

Rehabilitation: Physical therapy, speech therapy, occupational therapy.

17.Huntington's chorea clinic, course, prognosis.

Huntington's Disease (HD):

Etiology and Pathogenesis

HD is a hereditary, autosomal dominant neurodegenerative disorder caused by expansion of CAG trinucleotide repeats in the HTT gene.

Characterized by progressive degeneration of neurons in the basal ganglia (especially caudate nucleus) and cerebral cortex.

Polyglutamine tract expansions in huntingtin protein lead to toxic gain of function, causing neuronal death.

Clinical Features

Age of onset: typically 30-50 years; juvenile onset (<20 yrs) is less common (~10%).

Symptoms include:

Motor:

Early: chorea - involuntary, jerky, irregular movements starting distally.

Later: progression to dystonia, rigidity, and bradykinesia; gait instability; facial masking.

Speech and swallowing difficulties develop over time.

Cognitive: progressive decline in executive function, memory, and attention. Dementia occurs in advanced stages.

Psychiatric: depression, irritability, apathy; later hallucinations and psychosis possible.

Juvenile HD often has a more rapid progression and predominance of rigidity and bradykinesia rather than chorea.

Course and Prognosis

Disease usually progresses over 15-25 years.

Most patients develop profound disability.

Common cause of death: aspiration pneumonia.

Juvenile onset is more aggressive, with life expectancy around 5-10 years.

Diagnosis

Clinical: triad of chorea, cognitive decline, and psychiatric symptoms.

Genetic testing confirms CAG repeat expansion.

Imaging: caudate and putaminal atrophy on MRI.

Treatment

No cure; treatment is symptomatic.

Dopamine depleting agents (tetrabenazine) and antipsychotics for chorea.

Antidepressants and mood stabilizers for psychiatric symptoms.

Speech and physical therapy improve function.

Experimental therapies and gene therapies under investigation.

18.Hepatolenticular degeneration: clinical forms, diagnosis care.

Hepatolenticular Degeneration (Wilson's Disease)

Etiology

Genetic disorder caused by mutation in theATP7B gene leading to impaired copper metabolism.

Autosomal recessive inheritance.

Results in copper accumulation primarily in liver, brain (basal ganglia), eye, kidneys.

Clinical Features

Onset: Usually between ages 5 and 50, with variations.

Hepatic manifestations (more common in younger patients):

Chronic hepatitis, cirrhosis.

Hepatic failure, hemolytic anemia due to copper release.

Neurological manifestations (often later onset):

Movement disorders: tremor, chorea, dystonia, rigidity, ataxia.

Speech difficulties: dysarthria.

Psychiatric symptoms: cognitive decline, personality changes, depression, psychosis.

Other possible involvement: renal tubular dysfunction, cardiac abnormalities, arthritis.

Ophthalmic sign: Kayser-Fleischer rings (copper deposits in Descemet’s membrane), seen in 95% of neurological cases.

Diagnosis

Clinical presentation and examination for Kayser-Fleischer rings (slit lamp).

Laboratory investigations:

Low ceruloplasmin (<0.2 g/L) – may be normal in some.

Decreased serum copper.

Increased “free” (non-ceruloplasmin bound) copper.

Elevated 24-hour urinary copper excretion.

Imaging: MRI shows basal ganglia abnormalities.

Liver biopsy for copper quantification (>250 µg/g dry weight diagnostic).

Genetic testing forATP7B mutations.

Treatment

Chelation therapy:

D-Penicillamine – binds copper for excretion.

Trientine – alternative chelator.

Zinc preparations to reduce copper absorption.

Dietary copper restriction (avoid shellfish, nuts, chocolate, liver).

Early diagnosis and lifelong treatment are essential to prevent irreversible damage.

Liver transplantation in cases of liver failure.

Prognosis

Without treatment, progressive worsening and death.

With treatment, symptoms can be controlled, especially if started early.

19.Classification of diseases of the peripheral nervous system. Neuropathy, classification.

Classification of PNS Diseases

By Site:

Nerve roots/plexuses: Radiculopathies, plexopathies

Peripheral nerves: Mononeuropathies (single nerve), Polyneuropathies (multiple nerves)

Cranial nerves: Cranial neuropathies

By Cause:

Traumatic (injury/vertebrogenic)

Infectious (viral, bacterial)

Toxic (alcohol, chemicals)

Metabolic (diabetes)

Autoimmune (Guillain-Barré Syndrome)

Hereditary (Charcot-Marie-Tooth disease)

Vascular and nutritional

Neuropathy Classification

Mononeuropathy: Single nerve damage (e.g., carpal tunnel)

Multiple mononeuropathy (mononeuritis multiplex): Multiple separate nerves affected, often asymmetrically

Polyneuropathy: Many nerves affected symmetrically, often distal first (stockingglove pattern)

Axonal (primary damage to nerve fibers)

Demyelinating (primary damage to myelin)

Mixed type

By FiberType Involved:

Sensory neuropathy (sensation)

Motor neuropathy (movement)

Autonomic neuropathy (involuntary functions)

Mixed neuropathy

20.Guillain's acute inflammatory demyelinating polyneuropathy Barre. Clinic, diagnosis, course, treatment.

Guillain-Barré Syndrome (GBS), also known as acute inflammatory demyelinating polyneuropathy (AIDP), is an acute autoimmune disorder affecting the peripheral nervous system. It was first described by Guillain, Barré, and Strohl in 1916 and is classified under acute post-infectious polyneuropathy.

Clinical Features

Begins with general weakness, mild fever, paresthesias (numbness, tingling) in fingers and toes, and pain along peripheral nerves.

Weakness starts in the lower limbs and ascends to upper limbs, progressing from paresis to paralysis, involving both distal and proximal muscles.

Tendon reflexes decrease or disappear, muscle atrophy occurs.

Cranial nerves, especially facial nerves, may be affected.

Mild sensory disturbances and nerve trunk tenderness.

Vegetative symptoms include skin color changes, swelling, and hyperhidrosis.

Cerebrospinal fluid (CSF) shows characteristic protein-cell dissociation (high protein, normal cell count).

Four clinical forms include acute inflammatory demyelinating polyneuropathy (most common), chronic inflammatory demyelinating polyradiculoneuropathy, multifocal motor axonal neuropathy, and Miller Fisher syndrome (ophthalmoplegia, areflexia, ataxia).

Diagnosis

Clinical presentation: acute onset of symmetric weakness ascending over 2-4 weeks with sensory symptoms and areflexia.

CSF analysis: Elevated protein with normal white cell count (protein-cell dissociation).

Electromyography (EMG) and nerve conduction studies showing demyelination.

Differential diagnosis excludes myelitis, myopathy, spinal amyotrophy, poliomyositis, poliomyelitis, and tabes dorsalis.

Course

Progression of weakness over 2-4 weeks, followed by a plateau phase and gradual recovery.

Recovery starts with sensory function, then motor function, and finally reflexes.

Most recover within 2-3 months, but some may have persistent deficits.

Severe cases can result in respiratory failure and death.

Treatment

Immediate hospitalization, intensive care if vital functions are compromised.

Respiratory support including intubation and mechanical ventilation if needed.

Specific treatments include plasmapheresis and intravenous immunoglobulin (IVIG) therapy.

Supportive therapy with antihistamines, B vitamins, neuromidin, and prozerin.

Rehabilitation with physical therapy, massage, passive movements, and adjunct therapies like electrical stimulation and acupuncture during recovery.

21.Diabetic neuropathy: pathogenesis, variants, diagnosis, treatment

Diabetic neuropathy (DN) is a common complication of diabetes mellitus characterized by degenerative damage to peripheral nerves. It manifests in various clinical forms affecting sensory, motor, and autonomic nerves.

Pathogenesis

Chronic hyperglycemia leads to excess glucose entering peripheral nerve cells.

The polyol pathway is activated, converting glucose into sorbitol and fructose via aldose reductase.Accumulation of sorbitol causes osmotic and oxidative stress, damaging neurons, Schwann cells, and nerve vasculature.

Advanced glycation end-products (AGEs) form from non-enzymatic glycation of nerve proteins, impairing axonal transport, neuron metabolism, and causing inflammation.

Microvascular damage (endoneural microangiopathy) reduces blood flow and causes hypoxia.

Oxidative stress, mitochondrial dysfunction, protein kinase C activation, and inflammatory cytokines contribute to nerve injury and impaired regeneration.

Classification

1.Subclinical: asymptomatic detected by electrodiagnostic tests.

2.Clinical:

Diffuse distal symmetric sensorimotor neuropathy (sensory, motor, or mixed).

Autonomic neuropathy affecting cardiovascular, gastrointestinal, urogenital systems.

3.Focal/local neuropathies:

Mononeuropathies (single nerves), multiple mononeuropathies.

Plexopathies, radiculopathies.

Tunnel syndromes (nerve compressions).

Clinical Features

Gradual loss of sensation (hypoesthesia) starting in feet/hands ("stocking-glove" pattern).

Impaired vibration sense and proprioception leading to sensory ataxia.

Muscle weakness, atrophy, diminished reflexes.

Autonomic symptoms: orthostatic hypotension, gastroparesis, bladder dysfunction, erectile dysfunction.

Complications include trophic ulcers, tissue gangrene, diabetic foot syndrome with deformities (Charcot’s foot).

Diagnosis

Clinical exam: sensory testing, tendon reflexes.

Electrophysiological studies for nerve conduction.

Autonomic function tests.

Regular foot inspection to detect skin changes and ulcerations.

Treatment for diabetic neuropathy is multifaceted, focusing on blood sugar control, nerve protection, pain management, wound care, and prevention of complications—especially diabetic foot syndrome.

Treatment:

Glycemic Control

Intensive insulin therapy and strict blood glucose management slow progression and risk of neuropathy.