Neurodegenerative Diseases & Alzheimer's

• Neurodegenerative diseases involve the progressive loss of neuron structure or function, which includes neuron death.
• These diseases cause problems with movement or mental function.

Types of Neurodegenerative Diseases

• Alzheimer's Disease.
• Parkinson's Disease.
• Huntington's Disease.
• Amyotrophic Lateral Sclerosis.

Alzheimer's Disease

• Alzheimer's is an irreversible, progressive neurodegenerative disease that slowly destroys memory and thinking skills.
• Dr. Alois Alzheimer first described the disease in 1906 in one of his patients.

Gross Features of Alzheimer's

• Varying degrees of cortical atrophy accompanied by widening of the cerebral sulci is commonly observed in the frontal, temporal, and parietal lobes.
• Significant atrophy results in compensatory ventricular dilatation as a secondary effect of parenchyma loss.

Progression of Alzheimer's

• Mild Cognitive Impairment has a duration of 7 years and begins in the medial temporal lobe, characterized by short-term memory loss.
• Mild Alzheimer's has a duration of 2 years, spreading to lateral temporal and parietal lobes, causing reading problems, poor object recognition, and a poor sense of direction.
• Moderate Alzheimer's has a duration of 2 years, spreading to the frontal lobe, resulting in poor judgement, impulsivity and short attention span.
• Severe Alzheimer's has a duration of 3 years, when the disease spreads to occipital lobes, patients experience visual problems.

Cause of Alzheimer's Disease

• Alzheimer's is caused by a combination of genetic, lifestyle, and environmental factors that affect the brain over time.
• The exact cause is unknown, but Alzheimer's patients tend to have abnormal amounts of proteins (amyloid plaques) and fibers (tau tangles) in the brain.

Pathophysiology of Alzheimer's Disease

• The disease attacks nerve and brain cells and neurotransmitters.
• Destruction of nerve and brain cells causes clumps of protein, known as "plaques", and "bundles" (tau tangles), to form around brain cells.
• The presence of plaques and bundles destroys connections between cells, worsening the condition.
• Amyloid plaques are composed primarily of beta-amyloid proteins, which are derived from a parent protein called amyloid precursor protein (APP).
• Three secretase enzymes—alpha, beta, and gamma-secretase—cleave APP into soluble fragments that are then cleared away.
• Amyloid plaques form when beta- and gamma-secretase enzymes inappropriately cleave APP, leading to insoluble beta-amyloid proteins that accumulate to form plaques in the brain causing neurotoxicity and cell death.
• Neurofibrillary tangles are aggregates of overphosphorylated tau proteins.
• Tau proteins contain phosphate molecules.
• In Alzheimer's disease (AD), these proteins are hyperphosphorylated, causing the tau proteins to twist around, forming insoluble tangles that disrupt neuronal transport.

Parkinson's Disease

• Parkinson's is a chronic, progressive, neurodegenerative movement disorder.
• The disease primarily causes the death of nerve cells in the substantia nigra area of the brain.
• Parkinson's is characterized by a loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc).

Epidemiology of Parkinson's

• The onset of Parkinson's disease (PD) varies, but typically occurs between 50 and 80 years of age.
• The prevalence of PD is about 100 cases per 100,000 population, with an annual incidence of about 20 cases per 100,000.
• An estimated 100,000 Americans over the age of 65 have PD.

Morphology of Parkinson's

• Pathologic examination shows pallor of the substantia nigra.

Symptoms of Parkinson's

• Tremors of the hands occur even at rest.
• Persistent tremors are typical.
• Shuffling gait, unbalanced and in small steps, walks curved in a very characteristic way

Diagnosis of Parkinson's

• Results of computed tomography (CT), magnetic resonance imaging (MRI), and cerebrospinal fluid analysis are not useful in diagnosis.
• Positron-emission tomography (PET) scans using radio-labeled dopa can help confirm a diagnosis.
• CT and MRI are useful to eliminate other disease processes like tumors, strokes, hydrocephalus.

Pathology of Parkinson's Disease

• Lewy bodies can be seen in the neurons of people with Parkinson's disease.

Treatment of Parkinson's Disease

• There is no cure for Parkinson's disease, but medications, surgery, and multidisciplinary management can relieve symptoms.
• Levodopa and dopamine agonists are the main family of drugs used to treat motor symptoms.

Meningitis Definition

• Meningitis is an acute inflammation of the meninges
• It can be caused by bacteria or viruses

The Meninges

• The meninges are tissue layers that separate the skull and the brain.
• The Meminges from outer most to inner most are Dura mater, Arachnoid Layer, Pia Mater.

Route of Entry of Meningitis in CNS

• Skull or Back bone Fractures (trauma)
• Medical Procedures like Lumber Puncture,
• It can enter along peripheal nerves
• It an enter by blood of lymphatic system

Etiology of Meningitis

• Bacterial Infections
• Viral Infections
• Fungal Infections
• Inflammatory diseases(SLE)
• Cancer
• Trauma to head or spine

Pathophysiology of Meningitis

• Bacteria enters blood stream from trauma
• Enters the muscosal surface /cavity
• Causes breakdown of normal barriers
• Crosses the blood brain barrier
• Causes Proliferation in CSF(Cerebral Spinal Fluid)
• Which leads to Inflamation of the meninges
• Increase in ICP

Bacterial Meningitis

• It is also known as septic meningitis.
• It requires immediate attention.
• It can lead to permanent damage of bain and death.
• Spreads by coughin or sneezing

Bacterial Meningitis Treatment

• Antibiotics (per causative organism)
• Streptococcus Pneumonia 30-80%

Tubercular Meningitis

• Is caused by Mycobacterium tuberculi.
• Infection with the particular bacterium begins usually in the lungs.
• Dissimilar additional types of meningitis its progresses very slowly and symptoms are vague.

Viral Meningitis

• Causative agents for this condition are: Enterovirus, Measles virus, Herpes simplex virus.

Fungal Meningitis

• Is much less common then the others Infections.
• It is rare in healthy people but is more likely in persons who have impaired systems.

Meningitis Preventive Factors

• Vaccinations are a preventive factor like TB and Measles
• Seasonal Vaccinations also are helpful

Meningitis Clinical Manifestations

• Fever, possibly with cold hands & feet
• Refusing feeds or vomiting
• Neck retraction with arching of back
• Blank & staring expression
• Light Sensitivity
• Drowsiness or confusion
• Joint point
• Fitting

Meningitis Diagnosis

• History taking
• Physical assessment
• CT angiography and MRI
• Blood culture and sensitivity
• Lumbar Puncture : Elevated WBC, Elevated protein in the fluid from the test, Decreased glucose

Meningitis Diagnoses KERIG'S SIGN

• Severe neck stiffness
• A condition where severe stiffness of the hamstrings causes severe back pain and
• Inability to straighten the leg when the hip flexed to 90 degrees.
• And the other knee flex

Meningitis Diagnoses BRUDZINKI'SIGN

• Severe neck stiffness causes a patient's hips and knees to flex when the neck is flexed and back pain.

Meningitis Complications

• Sensori-neural hearing loss
• Epilepsy/Seizures
• Memory loss
• Paralysis
• Learning difficulty
• Death

Meningitis Management

• Bacterial Meningitis: Antibiotics
• Tuberular ATT medications
• Viral Cortisone fluid therapy and muscle relaxants.
• Seizure management:
• Cortisone Dehydration
• Shock can be treated with fluid therapy, Phenytoin, and muscle relaxants for seizure management.

Meningitis Physiotherapy Treatment Aims

• Chest care
• Normalization of tone
• Facilitation of ambulation
• Improve ROM
• Prevent DVT(deep vein thrombosis)
• Improve functional activities and Prevent bed sores.

Demyelinating Disorders

• Demyelinating disorders include conditions like Guillain-Barré Syndrome and Multiple Sclerosis
• Multiple sclerosis (MS) is an autoimmune demyelinating disorder characterized by distinct episodes of neurologic deficits.
• It is the most common of the demyelinating disorders.
• The disease appears clinically at 20-40 and Women are affected 3 times as often as are men

Progression of MS

• In most patients with MS, the clinical course of the illness evolves as relapsing and remitting episodes of neurologic deficit followed by gradual, partial recovery of neurologic function.
• The frequency of relapses tends to decrease during the course of time, but there is a steady neurologic deterioration in most patients.

Pathogenesis of MS

• Lesions of MS are caused by a cellular immune response that is directed against the components of the myelin sheath.
• The likelihood of developing this autoimmune process is influenced by genetic and environmental factors (microbial triggers).
• The disease is initiated by T cells and macrophages that react against self myelin antigens and secrete cytokines, such as IFN-y, that activate macrophages.
• Demyelination is caused by these activated macrophages in the presence of Imuglobulins.
• Oligodendroglia are not primarily affected and may even multiply to remyelinate the periphery of the lesion the first time.
• With time, oligodendroglia and remyelination decrease and astrocytes proliferate to form glial "scar" tissue.

Types of MS

• Types include Secondary progressive MS, Chronic progressive MS and Benign MS.

Morphology of MS

• Lesions appear as multiple, well-circumscribed, somewhat depressed, glassy, gray-tan, irregularly shaped plaques.
• In the fresh state, these plaques have a firmer consistency than the surrounding white matter (sclerosis).
• The size of lesions varies considerably.

Plaques in MS

• Plaques commonly occur beside the lateral ventricles and may be demonstrated to follow the course of paraventricular veins.
• Plaques are also frequent in the optic nerves.
• In active plaques, there is evidence of ongoing myelin breakdown with abundant macrophages containing lipid-rich, Inflammatory cells.
• Lymphocytes and monocytes are present, mostly as perivascular area.
• In quiescent plaques, there is a diminution of the inflammatory cell infiltrate and of macrophages.
• Little to no myelin can be found.
• There is a reduction in the number of oligodendrocyte nuclei.
• Astrocytic proliferation and gliosis are prominent.

Clinical Features of MS

• Unilateral visual impairment during the course of a few days, due to involvement of the optic nerve (optic neuritis) is a frequent initial manifestation of MS.
• Involvement of the brainstem produces cranial nerve signs, ataxia, nystagmus.
• Spinal cord lesions give rise to motor and sensory impairment of trunk and limbs, spasticity, and difficulties with the voluntary control of bladder function.

MS Diagnosis

• Diagnosed by MRI scans and Spinal tap(Lumbar Puncture)
• For presence of IgG antibody, macrophages and lymphocytes

Guillain-Barré Syndrome (GBS)

• The immune system attacks peripheral nerves' myelin sheath, leading to inflammation and demyelination.
• The condition begins in the feet and legs, progressing upwards and may affect respiratory muscles in severe cases.
• Symptoms include Weakness and tingling, loss of reflexes, muscle pain, respiratory distress.

GBS Diagnosis and Management

• Detailed neurological examination and tests such as nerve conduction studies and lumbar puncture.

GBS Rehabilitation and Recovery

• Physical Therapy: Exercises to improve muscle strength and coordination.
• Respiratory Support: Mechanical ventilation in severe cases to assist breathing.

Clinical Presentation

• MS often has a relapsing-remitting course, while GBS typically has a rapid onset and ascending progression.
• MS primarily affects the central nervous system, while GBS affects the peripheral nervous system.
• MS is a chronic condition with variable progression, while GBS often leads to rapid recovery with residual deficits in some cases.