MOTOR NEURON DISEASE

MOTOR NEURON DISEASE:

MOTOR NEURON DISEASE

Motor Neuron Disease:

Motor Neuron Disease The motor neuron diseases (MND) are a group of progressive neurological disorders that destroy motor neurons, the cells that control voluntary muscle activities .

Motor Neuron Disease:

Motor Neuron Disease Progressive involvement of UMN and LMN without sensory and bladder involvement (degeneration of pyramidal fibres, cranial motor nuclei and anterior horn cells)

Types:

Types Amyotrophic lateral sclerosis (ALS) Progressive Muscular Atrophy (PMA) Progressive Bulbar Palsy Primary Lateral Sclerosis (PLS) Pseudobulbar palsy

Amyotrophic lateral sclerosis :

Amyotrophic lateral sclerosis UMN weakness in lower limbs. LMN weakness in the upper limbs Brisk reflexes Bilateral pyramidal tract signs Extensor plantars

Progressive Muscular Atrophy:

Progressive Muscular Atrophy Progressive LMN weakness in the upper limb muscles Reflexes absent Lower limbs may be spared

Primary Lateral Sclerosis :

Primary Lateral Sclerosis Spastic paraparesis

Progressive bulbar palsy:

Progressive bulbar palsy Progressive LMN weakness of tongue and bulbar muscles Wasting and fibrillation of tongue Weakness of pharyngeal and laryngeal muscles Patient will present with dysphagia, dysphonia Gag reflex will be absent

Pseudobulbar palsy :

Pseudobulbar palsy Progressive bulbar palsy (UMN) Exaggerated gag reflex Emotional liability like crying, laughing without any stimulus

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MND in the presence of both upper and lower motor neuron degeneration is Amyotrophic Lateral Sclerosis . Where the illness affects only the upper motor neuron it is Primary Lateral Sclerosis . Where the illness affects only the lower motor neuron it is Progressive Muscular Atrophy .

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Progressive bulbar palsy is degeneration of the lower motor neurons innervating the bulbar region (mouth, face, and throat). Pseudobulbar palsy refers to degeneration of the upper motor neuron to the same region.

Lab studies:

Lab studies The diagnosis of MND is a clinical one Hemogram Serum B 12 levels ESR VDRL HIV ELISA

Neuro Investigations:

Neuro Investigations MRI study to rule out alternative diagnosis Motor sensory nerve conduction study normal Electro Myography (EMG) to distinguish from PLS from ALS Lumbar Puncture (LP) to rule out other causes

Prognosis:

Prognosis MND is typically fatal within 2-5 years. Around 50% die within 14 months of diagnosis. The remaining 50% will not necessarily die within the next 14 months As a rough estimate, 1 in 5 patients survive for 5 years, and 1 in 10 patients survive 10 years Major complications – Aspiration due to pharyngeal muscle disorder

Treatment:

Treatment Currently there is no cure for ALS. The only drug that affects the course of the disease is Riluzole The drug functions by blocking the effects of the neurotransmitter glutamate, and is thought to extend the lifespan of an ALS patient by only a few months Muscle relaxants (Tizanidine, Baclofen)

MOTOR NEURON DISEASE:

MOTOR NEURON DISEASE

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unknown cause Progressive degeneration of motor neurons in spinal cord, cranial nerve nuclei in brain stem and pyramidal neurons in motor cortex Incidence 1-3/100000 & Prevelance 3-5/100000 5% familial : Ch.21 ; SOD 1 defect & 95%- have possible cause like viral infection, trauma, exposure to toxins.

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Presence of combination of lower and upper motor neuron signs without sensory involvement Brisk reflexes with wasting and fasciculations : typical of MND

CLASSIFICATION:

CHRONIC a) UMN & LMN:- Amyotrophic lateral sclerosis b) Predominantly UMN :- Primary lateral sclerosis c) Predominantly LMN - Progressive muscular atrophy (spinal nu) Progressive bulbar palsy (cranial nv nu) CLASSIFICATION

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Associated with other degenerative disorder : Secondary motor neuron disorder

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B) ACUTE Poliomyelitis Herpes Zoster Coxsackie virus

GENETIC MND:

GENETIC MND A) UMN & LMN Familial ALS – AD,AR, Mitochondrial B) X linked spino bulbar muscular atrophy GM – 2 Gangliosidosis – Adult Tay sach’s

:

C) UMN Familial spastic paraplegia AD, AR, X linked D) ALS ALS + fronto temporal dementia Amyotrophy with behaviour disorder and parkinsonism features

AMYOTROPHIC LATERAL SCLEROSIS:

AMYOTROPHIC LATERAL SCLEROSIS Most common form of progressive MND Death of both LMN and UMN or cortico spinal motor neuron At onset, selective LMN or UMN, later involve both

Pathology:

Pathology Motor neuron under go shrinkage due to lipofuscin deposition and later death with proliferation of astroglia and microglia Death of motor neuron in brain stem and spinal cord  degeneration  consequent atrophy of corresponding muscle fibre diagnosed on muscle biopsy  amyotrophy

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Loss of motor cortical neuron  thinning of cortico spinal tract  loss of fibre in lateral column  fibrillary gliosis  lateral sclerosis “Selectivity of neuronal cell death” External ocular muscles and sphincters remain intact ( parasympathetic neuron in sacral spinal cord)

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Onset : > 50 yrs ; less common before 30 yrs age. Males > females

Clinical features:

Clinical features Depends on involvement of neurons but Pyramidal tract features common . Cramping pain : common Distal and proximal muscle weakness and wasting ; Wasting out of proportion to weakness Fasciculations Spasticity,exaggerated reflexes Extensor plantar reflexes.

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Bulbar palsy Involvement of respiratory muscle  death Pseudo bulbar effect – degeneration of cortico bulbar projection innervating brain stem Sensory, bowel , bladder and cognitive functions are preserved Dementia can be seen in familial

Diagnostic guidelines:

Diagnostic guidelines Spontaneous UMN and LMN involvement with progressive weakness and exclusion of all alternative diagnosis Involvement : bulbar / cervical/thoracic / lumbosacral

Familial ALS :

Familial ALS Autosomal dominant Clinical features same Due to mutation in gene encoding, cytosolic Cu and Zn binding enzymes, SOD –1 Pathogenesis - increased excitotoxic transmitters such as glutamate  death

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Treatment – Riluzole 100 mg / day  decrease glutamate release - Side effects – nausea, dizziness, weight loss and elevated liver enzymes Foot drop splint Finger extensor splint Respiratory support Gastrostomy - bulbar disease

SELECTED UMN DISORDERS:

SELECTED UMN DISORDERS 1. Primary lateral sclerosis Rare disorder Onset – adult life Pathology – selective loss of large pyramidal cells in precentral gyrus. Degeneration of cortico spinal and cortico bulbar projections Peripheral motor neuron and other neuronal systems spared

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Clinical features - Progressive spastic weakness of limbs - Spastic dysarthria, dysphagia - Fasciculations, amyotrophy and sensory changes will be absent Course - variable

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2) Familial spastic paraplegia Autosomal dominant Onset – 3 rd –4 th decade Pathology – degeneration of cortico spinal tract shows atrophy of more caudal level in spinal cord. Clinical features - Progressive spastic weakness beginning distal lower extremities

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Long survival – respiratory function spared Late illness- urinary and faecal incontinence Pure form of FSP – ataxia, posterior column sensory loss and amyotrophy are absent. In some patients, sensory changes present.

AETIOLGY AND INVESTIGATIONS OF MND:

AETIOLGY AND INVESTIGATIONS OF MND a) Structural lesion - Para sagittal and foramen magnum tumour, cervical spondylosis, CV junction anomaly , spinal cord AV malformation Inv :- MRI scan of head with cervical spine

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b) Infection - Bacterial – Tetanus, Lyme disease - Viral – Poliomyelitis, Herpes zoster, retroviral myelopathy Inv :- CSF examination, culture, Lyme antibody titre, anti viral antibody titre and HTLV –1 titre

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c) Intoxicants and physical agents - Toxins – Lead, aluminium - Drugs – Strychnine, phenytoin - Electric shock and irradiation Inv :- 24 hour urine for heavy metals, serum for lead levels

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d) Immunologic mechanism - Plasma cell dyscrasia - Auto immune poly radiculopathy, motor neuropathy with conduction block Inv :- CBC, ESR, Protein immuno electrophoresis , anti GM –1 antibodies

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e) Para neoplastic - Lymphoma - Inv :- MRI scan, bone marrow biopsy f) Metabolic - Hypoglycemia, Hyperparathyroidism , hyperthyroidism , vit B12 , folate and vit E deficiency, Mitochondrial dysfunction and malabsorption

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Inv:- FBS, serum Na + , K + , Ca 2+, PTH, Ca phosphate, TFT , Vit B12 , vit E and folate levels, 24 hr stool fat, fasting lactate , pyruvate and ammonia

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g ) Hereditary biochemical disorders - Superoxide dismutase 1 gene mutation – WBC DNA analysis - Androgen receptor defect (Kennedy disease) – abnormal CAG insert in androgen receptor gene

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- Hexasaminidase deficiency – Lysosomal enzyme screen - Hyperlipidemia – Lipid electrophoresis - Hyper gylycinuria – Urine and serum aminoacid

Poliomyelitis:

Poliomyelitis

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Acute viral infection caused by an RNA virus. Infection of human GIT, and rarely CNS

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Poliomyelitis: Greek translation is “Gray Matter.” Attacks gray nerves in spinal cord first and cuts off the impulses that travel from brain to muscles and eventually causes muscles fibers to shrivel and die. Childhood disease but attacks adults as well. 3 stages: acute, convalescent, chronic

INDIA :

INDIA Over all reduction by 99.06% from 1988 to 2000 Delhi, Bihar, UP and West Bengal.-

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Its an eradicable disease Long term carrier state is not known to occur.

Epidemiological trends:

Epidemiological trends It can occur sporadically endemically epidemically.

Agent factors:

Agent factors Polivirus serotype 1,2 and 3. Paralytic polio by type 1. Faeco-oral route. Man – only reservoir Most infections are subclinical. Mild and subclinical case – spread of infection. Cases are most infectious 7-10 days before and after the onset of symptoms. Excreted in faeces for 2-3 weeks ( 3-4 months)

Host factors:

Host factors Disease of infancy and childhood. ( 6 months –3 yrs) M:F-3:1 Fatigue , trauma, im inj, tonsillectomy- risk for paralytic polio. Life long immunity, but reinfection can occur as infection with 1 type does not protect against the others.

Environmental factors:

Environmental factors Rainy season. 60 % of cases occur June to september . Contaminated water , food and flies. Over crowding and poor sanitation.

Mode of transmission:

Mode of transmission Faeco-oral route Droplet infection.

Incubation period:

Incubation period 7-14 days

Clinical spectrum:

Clinical spectrum Subclinical infection.-95% Abortive polio or minor illness. –4-8% Non paralytic polio.- 1 % Paralytic polio. < 1 %.

Prevention.:

Prevention. Immunization is the sole effective means of preventing poliomyelitis. Both killed and live attenuated.

Vaccines:

Vaccines Inactivated (Salk polio vaccine) Oral (Sabin polio vaccine ).

Salk vaccine:

Salk vaccine All serotypes 4 doses First 3 doses are given at an interval of 1-2 months and fourth dose 6-12 months.. Booster dose prior to school entry and every 5 yrs till age 18.

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Induces humoral Abs, but no intestinal or local immunity Prevents paralytic polio But do not prevent reinfection of the gut by wild viruses. Not recommended during epidemics.

Sabin (OPV):

Sabin (OPV) Sabin in 1957. Contains live attenuated virus (1,2&3) grown in primary monkey kidney or human diploid cell cultures

National immunization schedule:

National immunization schedule Primary course of 3 doses at one month interval ,starting at 6 weeks. 3 drops using dropper provides both local and systemic immunity.

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Salk OPV Killed formolised virus Live attenuated virus S/c or IM orally No local immunity Humoral & local Prevent paralysis Prevents paralysis and intestinal reinfe Not in epidemics Very useful Difficult to manufacture easy costlier Cheaper Longer shelf - life Requires to be stored & transported at < 0 temp

Post polio syndrome:

Post polio syndrome A condition that manifest in survivors of polio 10 to 40 years after they have recovered. It is caused in part by the dying off of the nerve ending in the motor units that survived first attack. Symptoms included: fatigue, muscle weakness, joint pain, and atrophy of infected muscles