DEGENERATIVE DISEASE OF THE BRAIN

1. DEGENERATIVE DISEASE OF THE BRAIN Dr. Alka Stoelinga

2. PARKINSON’S DISEASE • Parkinsonism is a chronic and progressive clinical syndrome resulting from deficiency of the neurotransmitter dopamine as a consequence of degenerative, vascular, or inflammatory changes in basal ganglia. • Parkinsonism is characterized • Bradykinesia • Rigidity • Instability (Postural) • Tremor at rest/ resting tremor • (Mr. Parkinson is a fine BRITish gentleman) • Parkinson’s disease- • Incidence 1 to 2 per 1000 , 2 per 100 among people older than 65 years • Sex incidence –Equal, • Less in cigarette smoker. Dr. Alka Stoelinga

3. Etiology: • Idiopathic • Also called Paralysis agitans or Parkinson's disease • Poisoning • MPTP(Methyl-phenyl Tetrahydropyridine) causes severe parkinsonism • CO • Cyanide • Manganese • Drugs: • Neuroleptics • Haloperidol, Chlorpromazine • Antiemetics • Metoclopramide • Reserpine , alpha-methyldopa • Structural lesions around basal ganglia: • Trauma/ Tumor/ Abscess/ Infarct • Postencephalitic Parkinsonism Dr. Alka Stoelinga

4. Pathology • Loss of pigmented dopaminergic neurons in substantia nigra • Progressive cell degeneration in substantia nigra • Presence of neuronal eosinophilic inclusion bodies i.e., Lewy bodies • Atrophic changes • Reduction of dopaminergic output from substantia nigra to the globus pallidus resulting in inhibition of activation of cerebral cortex causing Bradykinesia. Dr. Alka Stoelinga

5. Positive Alpha-Synuclein staining of a Lewy body in a patient with Parkinson's disease PD is considered a synucleinopathy due to its abnormal accumulation of the alpha- synuclein protein in the brain in the form of lewy bodies as opposed to other diseases such as Alzheimer's disease where the brain accumulates tau protein in the form of neurofibrillary tangles. Dr. Alka Stoelinga

6. Dr. Alka Stoelinga

7. Parkinson’s disease Dr. Alka Stoelinga

8. Clinical features • Classical features consists of : • Bradykinesia (Slow movements, mask facies, reduction of automatic movements) • Rigidity (Cogwheel) • Instability (Postural) • Tremor (Resting). • Other nonspecific features are : • Tiredness, muscle aches, mental slowness, depression, Change in the hand writing may be the only features at early stage • In an advanced disease: • Tremor-coarse ,pin-rolling, resting as well as intentional tremor • Mask like face • Bradykinesia • Flexed posture • Gait –slow walking, shortened stride, reduced arm swing(Shuffling gait), tendency to run (festination gait), reduced arm swing, Impaired balance on turning • Glabellar tapping: Sustained blinking of eyes (Positive Myerson’s sign). • Speech: Soft, rapid, indistinct • Later stage: Impairment of intellectual function Dr. Alka Stoelinga

9. Dr. Alka Stoelinga

10. Dr. Alka Stoelinga

11. Parkinson’s disease Dr. Alka Stoelinga

12. Differential diagnosis: • Hypothyroidism • Depression • Drug induced parkinsonism • Multi infarct dementia • Alzheimer’s disease • Essential benign familial tremor • Wilson’s disease • Huntington’s disease • Corical basal ganglionic degeneration Dr. Alka Stoelinga

13. Diagnosis: Medical history and neurological examination Dr. Alka Stoelinga

14. Investigations • No specific investigations which can help diagnosis • Gold standard- Lewy bodies during autopsy • 3 Criteria required • First: Requires the person to suffer from slowness of movement (Bradykinesia) and either rigidity, rest tremor or postural instability. • Second: other possible causes for symptoms have to be ruled out • Third: The person would have to have 3 or more of the following during onset or evolution: • Unilateral onset • Rest tremor, • Progression • Asymmetry of motor symptoms • Response to levodopa during at least 5 years • Clinical course of at least ten years and • Appearance of dyskinesias induced by the intake of excessive levodopa. • Accuracy of diagnostic criteria evaluated at autopsy is between 75 and 90% Dr. Alka Stoelinga

15. PET scan shows decreased dopamine activity in the basal ganglia Dr. Alka Stoelinga

16. Management: • Treatment of parkinsonism is directed toward restoring the dopaminergic and cholinergic balance in the striatum by blocking the effect of Acetylcholine with Anticholinergics or by enhancing dopaminergic transmission. Dr. Alka Stoelinga

17. Management • Levodopa : • It is converted into dopamine after decarboxylation and thus replaces the dopamine deficiency in brain. • Start with 50 mg 8 hourly, and gradually increase the dose • S/E: Postural hypotension, nausea, vomiting, dystonias, hallucination, delusion are important side effects • To prevent the side effects or reduce the dose it is usually combined with Carbidopa or Benserazide. • Levodopa250mg+Carbidopa 25mg • Levodopa 250mg+ Banserazide 50mg • Late deterioration occurs in the form of wearing off effect ( end of dose) and on –off phenomenon Dr. Alka Stoelinga

18. Decarboxylase inhibitors(Carbidopa and Benserazide) : • Reduce side-effects by reducing peripheral conversion of levodopa to dopamine • Anticholinergic (Trihexyphenidyl/Benztropine) • Young patients with less bradykinesia • Reduces the over activity of acetylcholine in negrostriatal pathway. • Reduce tremor and rigidity. • ADR: Dry mouth, Blurred vision, urinary retention, confusion • Amantadine : • Rx of choice in age >60 • Enhances the release of dopamine at the nerve terminal. • Can be use in early disease. • Useful in Bradykinesia • Started early in the course. Dr. Alka Stoelinga

19. Dopamine receptor agonists (Bromocriptine, Pergolide, Cabergoline) • Act directly on striatal receptors. • Monoamine oxidase type B (MAO-B) inhibitor (selegiline) • Increases the availability of neuronal dopamine by reducing its metabolism. • Associated with many adverse effects. • Only drug in Parkinsonism that is thought to arrest the progression of disease • Catechol-O-methyl-transferase (COMT) inhibitor Entacapone : • Prolongs the availability of dopamine by inhibiting the metabolism of dopamine and levodopa outside the neuron. Dr. Alka Stoelinga

20. Surgery • Stereotactic thalamotomy • Fetal midbrain cells implantation (experimental) • Physiotherapy and speech therapy • Prognosis : • complications of immobility and tendency to fall Dr. Alka Stoelinga

21. HUNTINGTON’S DISEASE • Genetic degenerative brain disorder • Disease starts in adult life • Demonstrates “anticipation”: Younger age of onset in subsequent generation • Characterized by presence of HD gene located on chromosome 4p. • CAG trinucleotide repeat expansions that codes for protein called huntingtin. • HD mutation leads to abnormal cleavage of huntingtin protein  interferes nuclear mechanism cellular death. • Inherited in Autosomal dominant fashion Dr. Alka Stoelinga

22. Dr. Alka Stoelinga

23. Clinical features: • Starts in middle adult life • Progressively worsening chorea • Psychiatric symptoms • Dementia (Memory is preserved till later stages Lack of judgement, disinhibition, inattention associated with depression) • Poorly coordinated gait • Seizures • In juvenile variety: Parkinson like features Dr. Alka Stoelinga

24. Clinical Hallmark • Chorea (Fidgeting sudden movement of limbs or trunk) • Behavioral disturbances Dr. Alka Stoelinga

25. Diagnosis: • Ct scan/MRI head • DNA analysis- DNA repeat expansions Management: • No specific management • Symptomatic management • Treatment of chorea: Tetrabenazine • Genetic counseling Dr. Alka Stoelinga

26. ALZHEIMER’S DISEASE • Most common cause of dementia • Seen in patients >45 years • 5% of population >65years suffer from dementia Etiology: • Genetic • Atrophy:Cerebral cortex and Hippocampus • HPE: Senile plaque,neurofibrillary tangles • Neurotransmitter abnormality especially cholinergic neurotransmitters Dr. Alka Stoelinga

27. Clinical features: • Memory: Delayed recall • Short term memory more impaired • Apraxia: Characterized by loss of the ability to execute/carry out learned purposeful movements, despite having the desire and the physical ability to perform the movements. • Aphasia • Anosognosia: Denial of anything wrong • Acute worsening by Intercurrent illness • Depression Dr. Alka Stoelinga

28. Investigation: • CT/MRI head • EEG • Blood: CBC, ESR, Thyroid function test, ANA, Anti ds DNA,VDRL Management: • No definitive treatment • Cerebral cholinesterase inhibitors: Donepezil, Rivastigmine • Supportive treatment Dr. Alka Stoelinga

29. PICK’S DEMENTIA: • Degeneration of frontal and temporal lobes • Picks bodies in HPE • Dementia,Aphasia LEWY BODY DEMENTIA: • Similar to parkinson’s disease:Lewy bodies are found in cerebral cortex • Dementia,parkinson’s like features Dr. Alka Stoelinga

30. PRION DISEASE/CREUTZTELDT JAKOB DISEASE(CJD): • Due to prion:Infectious proteins • Can be sporadic/Genetic/Acquired • Characterized by progressive dementia,myoclonus and characteristic EEG • Variant of CJD: • seen in UK: Mad cow disease • Kuru diseae:Another disease Dr. Alka Stoelinga

31. BELL’S PALSY • This is common,acute,isolated facial nerve paralysis • Infection results in swelling of the nerve within the facial canal in the petrous bone. • Swelling is responsible for initial loss of nerve impulse conduction leading to facial paralysis. Causes: • Idiopathic • Due to reactive latent HSV-1,LMN Dr. Alka Stoelinga

32. Clinical feature: Symptoms: • Onset: Subacute,within few hours • Preceded by pain around the ear • Weakness or inability to move on one side of face • Numbness(without objective loss of sensation) • Hyperacusis • Loss of tear • Impairment of taste on the anterior 2/3rd of the tongue • Dribbling of saliva and water from the affected side • Collection of food in the mouth on paralyzed side Dr. Alka Stoelinga

33. Signs: • Loss of wrinkling on the affected half of forehead • Inability to close the eye • Bell’s Phenomenon: Upward rotation of the eyeball on trying to close the affected eye • Flattening of the nasolabial fold • Loss of retraction of the angle of the mouth, while showing his teeth Dr. Alka Stoelinga

34. Bell’s palsy Dr. Alka Stoelinga

35. Bell’s Palsy Dr. Alka Stoelinga

36. Management: Investigation: • EMG Mean action potential decreased Treatment: • No proven treatment • Steroid: • Prednisolone 60mg/d for 1 week • It reduce edema of the facial nerve,and may limit damage and speed recovery • Acyclovir • Both combined: Acyclovir+Prednisolone=More effective • Supportive treatment: • Artificial tear drop • Eye pad Dr. Alka Stoelinga

37. Prognosis: • Spontaneous recovery seen in 70-80% within 2-12 weeks Poor prognostic factors: • Severe pain at onset • Complete palsy at onset • Elderly patient • Decreased MAP after 1 week on EMG Dr. Alka Stoelinga

38. RAMSAY HUNT SYNDROME • Herpes zoster of geniculate ganglion causes facial palsy with herpetic vesicles in the external auditory meatus,this combination is called Ramsay hunt syndrome. Dr. Alka Stoelinga

39. TRIGEMINAL NEURALGIA • It is a neuropathic disorder of one or both of the facial trigeminal nerves. • It causes episodes of intense pain in any or all of the following: the ear, eye, lips, nose, scalp, forehead, teeth or jaw on one side of the face. • Exclusively seen in middle aged or elderly • Severe pain– for few seconds which occurs in paroxysms • TN brings about stabbing, mind-numbing, electric shock-like pain from just a finger's glance of the cheek or spontaneously without any stimulation by the patient. • Pain is brought on by stimulation of specific trigger zone in the face during: Washing,shaving,eating,talking,touching and cold wind may be the stimuli • Cause: Occasionally due to Herpes zoaster Dr. Alka Stoelinga

40. Management: • Exclude other causes • Medical therapy: • Carbamazepine • Phenytoin • Injection of trigeminal ganglion with alcohol or Phenol is a common procedure. • Radiofrequency thermal rhizotomy of trigeminal ganglion • Microvascular decompression in facial canal Dr. Alka Stoelinga