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UNDERSTANDING AND MANAGING VERTIGO Vijay Sardana MD,DM Professor & Head, Deptt. Of Neurology, Medical College, Kota

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Prevalence of Vertigo and Giddiness <ul><li>5% of patients visiting the GP </li></ul><ul><li>10% of patients visiting the </li></ul><ul><li>Otorhinolaryngologists </li></ul><ul><li>Life time prevalence-30% </li></ul><ul><li>3 rd most common symptom </li></ul>

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Vertigo Defination Illusion of spinning sensation of self or Surroundings, usually due to disturbance of vestibular system

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Vertigo:-Problems <ul><li>Vertigo patients are nobody’s baby </li></ul><ul><li>Shunting between GPs, Physician, Neurologist, ENT specialist and psychiatrists. </li></ul><ul><li>With or without investigations-it is vestibular </li></ul><ul><li>Suppressant. </li></ul><ul><li>Few dedicated physicians for vertigo. </li></ul>

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What causes vertigo ? Contradictory information from: Vestibular, Visual & proprioceptive system

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Causes of Dizziness Types of Dizziness Patients Experience Pathologic Causes Vertigo Illusion of movement of patients or Surroundings Disturbance of peripheral or CNS pathways of vestibular system Syncope or Presyncope Impending loss of consciousness Cerebral perfusion of brain falls below a critical level Disequilibrium A sense of imbalance Vestibular, Proprioceptive, Cereballer,Visiual III defined dizziness Emotional disorders Hyperventilation, Anxiety, Depression, Conversion reaction

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Vertigo Neuroanatomical & Neurochemical Basis <ul><li>Glutamate-Vestibular nerve fibers </li></ul><ul><li>Acetylcholine muscaranic recepters(m2)- </li></ul><ul><li>pons & medulla </li></ul><ul><li>GABA-Vestibular neurons </li></ul><ul><li>Histamine-diffusely in vestibular structures. </li></ul><ul><li>-H1& H2 receptors- Pre & </li></ul><ul><li>post synaptically on vestibular cells. </li></ul>

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Vertigo - Mechanisms <ul><li>Mechanism Known : </li></ul><ul><li>-Migraine </li></ul><ul><li>-Epilepsy </li></ul><ul><li>-Meniere’s disease </li></ul><ul><li>-Central causes </li></ul><ul><li>In most of case- no convincing scientific evidence of cause & mechanism. </li></ul>

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Vertigo <ul><li>Common “Peripheral Vertigo” </li></ul><ul><li>Benign positional vertigo </li></ul><ul><li>Vestibular neuronitis </li></ul><ul><li>Labyrinthitis </li></ul><ul><li>Meniers.s disease </li></ul><ul><li>Post traumatic vertigo </li></ul>

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Vertigo <ul><li>Central Vertigo </li></ul><ul><li>Vestibular portion of 8th nerve </li></ul><ul><li>Vestibular nuclei within brain stem </li></ul><ul><li>Central connections of vestibular nuclei- </li></ul><ul><li>*Cerebellar Floccules </li></ul><ul><li>*Visual sensory connections </li></ul><ul><li>*Afferent from joint & </li></ul><ul><li>tactile receptors </li></ul>

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Vertigo Central Vertigo-Characteristics <ul><li>Less common than peripheral & systemic causes. </li></ul><ul><li>Vertiginous symptoms usually less common. </li></ul><ul><li>Additional neurological science usually present. </li></ul><ul><li>Vertigo as a sole manifestation rare. </li></ul>

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Vertigo <ul><li>Peripheral </li></ul><ul><li>Short duration </li></ul><ul><li>Severe, often </li></ul><ul><li>paroxysmal </li></ul><ul><li>Accompanied by </li></ul><ul><li>auditory </li></ul><ul><li>symptoms </li></ul><ul><li>Fatiguilibility. </li></ul><ul><li>Reproducibility </li></ul><ul><li>inconsistent </li></ul><ul><li>Central </li></ul><ul><li>Chronic/Permanent </li></ul><ul><li>Less severe, </li></ul><ul><li>Continuous </li></ul><ul><li>S/S of brain stem/ </li></ul><ul><li>Cerebellum, </li></ul><ul><li>Auditory less freq </li></ul><ul><li>No fatiguilibility </li></ul><ul><li>Reproducibility </li></ul><ul><li>consistent </li></ul>

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Vertigo <ul><li>Peripheral </li></ul><ul><li>Nystagmus </li></ul><ul><li>- Unidirectional </li></ul><ul><li>- Horizontal-rotatory, </li></ul><ul><li>Never vertical </li></ul><ul><li>- Inhibited by visual </li></ul><ul><li>fixation </li></ul><ul><li>- Nystagmus with </li></ul><ul><li>Vertigo </li></ul><ul><li>Fall & past pointing- </li></ul><ul><li>towards side of lesion </li></ul><ul><li>Central </li></ul><ul><li>Nystagmus </li></ul><ul><li>- Uni/bidirectional </li></ul><ul><li>- Horizontal-rotatory, </li></ul><ul><li>vertical </li></ul><ul><li>- Not inhibited </li></ul><ul><li>- Sometimes only </li></ul><ul><li>Nystagmus, no vertigo </li></ul><ul><ul><li>Veriable </li></ul></ul>

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Vertigo <ul><li>Central Vertigo-Causes </li></ul><ul><li>Brainstem ischemia & infarction-VBI, infarction </li></ul><ul><li>in territory of Int.auditory artery (collegen </li></ul><ul><li>disorder), subclavian steel phenomenon. </li></ul><ul><li>Demylinating diseases-MS, postinfection demylination </li></ul><ul><li>CP angle tumors. </li></ul><ul><li>Cranial neuropathy(isolated 8 th nerv/multiple cranial </li></ul><ul><li>nerves)-vasculitis, granulomatous dis(sarcoidosis), </li></ul><ul><li>maningeal carcinomatosis. </li></ul>

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Vertigo <ul><li>Central Vertigo-Causes contd.- </li></ul><ul><li>Intrinsic Brainstem lesions. </li></ul><ul><li>Other posterior fossa lesions- cerebellar infarct, haematoma </li></ul><ul><li>Seizure disorder-CPS </li></ul><ul><li>Migraine-Basilar artery migraine, migranous aura </li></ul><ul><li>Degenerative heridofamilial-SCA-PSP </li></ul><ul><li>Cervical Vertigo-Neck trauma, irradiation to upper cervical </li></ul><ul><li>sensory roots, CVJ anomalies. </li></ul>

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Vertigo <ul><li>Common drugs producing vertigo </li></ul><ul><li>Anticonvulsant </li></ul><ul><li>-Barbiturates </li></ul><ul><li>-Phenytoin </li></ul><ul><li>-Carbamazepine </li></ul><ul><li>Alcohol </li></ul><ul><li>Salicylates </li></ul><ul><li>Cinchona alkaloids-quinine </li></ul><ul><li>Aminoglycosides </li></ul><ul><li>Alkalyting agents </li></ul>

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VERTIGO: Clinical evaluation <ul><li>Good history </li></ul><ul><li>- To diagnose – 90% </li></ul><ul><li>- bond/ relationship with patient </li></ul>

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Vertigo <ul><li>Clinical Evaluation </li></ul><ul><li>Complete medical history </li></ul><ul><li>Complete neurological examination </li></ul><ul><li>esp. nystagmus 5 th nerve including corneal </li></ul><ul><li>reflux,7 th ,8 th nerves, cerebellar signs & long </li></ul><ul><li>tract signs </li></ul><ul><li>Otological examination & related tests </li></ul><ul><li>CT head/MRI </li></ul><ul><li>EEG when indicated </li></ul>

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Vertigo-Treatment <ul><li>Specific treatment </li></ul><ul><li>Antimigraine drugs </li></ul><ul><li>Antiepileptic drugs </li></ul><ul><li>Salt restriction & diuretics in meniere’s disease </li></ul>

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<ul><li>I Want……. </li></ul><ul><li>Fewer attacks every month </li></ul><ul><li>When attacks occur they are not as bad as before </li></ul><ul><li>When attacks occur they do not last long </li></ul>

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Vertigo <ul><li>Symptomatic Treatment-Goals </li></ul><ul><li>Elimination of vertigo </li></ul><ul><li>Vestibular supression </li></ul><ul><li>Enhancement/non compromise of process of </li></ul><ul><li>vestibular compensation </li></ul><ul><li>Reduction of accompanying neurovegetative & </li></ul><ul><li>psycho affective signs(nausea,vomiting,anxiety) </li></ul><ul><li>Treatment of cause </li></ul>

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Vertigo <ul><li>Vestibular Suppression </li></ul><ul><li>Decrease in asymmetry in vestibular tone </li></ul><ul><li>Decrease in vestibular function in normal </li></ul><ul><li>& abnormal side both </li></ul>

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Vertigo <ul><li>Vestibular Suppressants </li></ul><ul><li>Anticholinergics -Homatropine </li></ul><ul><li>-Scopolamine(Hyoscine) </li></ul><ul><li>Antihistamines -Diphenhydramine </li></ul><ul><li>-Cyclizine </li></ul><ul><li>-Dimenhydrinate </li></ul><ul><li>-Meclizine </li></ul><ul><li>-Hydrocyzine </li></ul><ul><li>-Promethazine </li></ul><ul><li>-Cinnarizine </li></ul><ul><li>-Flunarizine </li></ul><ul><li>Benzodiazepines -Diazepam </li></ul><ul><li>-Lorazepam </li></ul><ul><li>-Clonazepam </li></ul>

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Vertigo <ul><li>Vestibular Compensation </li></ul><ul><li>Plasticity of the CNS </li></ul><ul><li>Sensory feedback (Vertigo) required </li></ul><ul><li>for compensation </li></ul><ul><li>2 goals (decrease in vertigo and increase </li></ul><ul><li>in compensation) often incompatible </li></ul>

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Vestibular Rehabilitation <ul><li>Adaptation </li></ul><ul><li>a phenomenon which helps a patient with persisting peripheral dysfunctional state to regain normal balance. </li></ul><ul><li>Habituation </li></ul><ul><li>repeated exposure of the body to “mismatched “ sensory input. </li></ul><ul><li>Compensation </li></ul><ul><li>a goal directed process induced by some recognized errors, directed towards its elimination </li></ul>Norre M E, Crit. Rev. Phy. Rehab. Med., 1990, 2, 2, 101-120, Kirtane MV, Ind. J. Otolaryngol HNS, 1999, 51 (2), 27-36.

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Vestibular compensation <ul><li>Right labyrinth damaged Left Labyrinth normal </li></ul><ul><li>Less electrical discharge Normal electrical discharge </li></ul><ul><li>Imbalance between two sides- Vertigo </li></ul><ul><li>Sensation of unequal inputs from two sides by CNS </li></ul><ul><li>Habituation and adaptation to the error </li></ul><ul><li>possible ways </li></ul><ul><li>increasing elect. discharge from Decreasing electrical discharge from </li></ul><ul><li>damaged labyrinth normal labyrinth </li></ul><ul><li>  </li></ul><ul><li>Not possible Cerebellar Clamp or Vestibular shutdown </li></ul>

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Acute compensation by cerebellar clamp or vestibular shutdown <ul><li>Cerebellum through connections with Vestibular nuclei induces reduction in resting electrical discharge- cerebellum induced vestibular shutdown </li></ul><ul><li>Reduces inequality between electrical discharge between the two sides by lowering electrical discharge of normal vestibular labyrinth </li></ul><ul><li>Advantages </li></ul><ul><li>symptomatic relief of vertigo in acute case </li></ul><ul><li>At rest, no vertigo </li></ul><ul><li>Disadvantage </li></ul><ul><li>reduced vestibular sensitivity </li></ul><ul><li>Inhibited vestibular system fails to react normally to vestibular assault </li></ul><ul><li>Sudden head movement leads to vertigo </li></ul>Chronic compensation is essential .

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<ul><li>Normal situation </li></ul><ul><li>Right vestibule equal Left vestibule </li></ul><ul><li>Right vestibular nuclei Left vestibular nuclei </li></ul><ul><li> </li></ul><ul><li> Vertigo </li></ul><ul><li>Right vestibule damaged Left vestibule normal </li></ul><ul><li>Less electrical normal electrical. Discharge discharge </li></ul><ul><li>Right vestibular nuclei left vestibular nuclei </li></ul>Chronic compensation for vertigo Biswas A, Neurotological Diseases IN ‘An Introduction to neurotology”, 1998, 85-7.

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Chronic Compensation <ul><li>Chronic compensation </li></ul>Right vestibule damaged Left vestibul normal normal electrical discharge Right vestibular nuclei Left vestibular nuclei equal synapse equal brain

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Chronic compensation <ul><li>Inhibitory effect of cerebellum on vestibular nuclei is gradually removed and requisite anatomical restructuring of central vestibular pathways takes place </li></ul><ul><li>Cerebellum monitors afferent ( sensory) and efferent (motor) inputs form the two sides </li></ul><ul><li>Vestibular nuclei on damaged vestibular side gets connected anatomically and functionally to vestibular nuclei on normal vestibular side. </li></ul><ul><li>Capacity of cerebellum to adapt to the affected or changed vestibular scenario is called plasticity of CNS. </li></ul>

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Chronic compensation <ul><li>Whole compensatory mechanism controlled by CNS , mediated by cerebellum. Compensatory mechanism ineffective if cerebellum malfunctioning, (Cerebellar degeneration) </li></ul><ul><li>If after the above compensatory mechanisms, still errors in vestibular functioning, corrected by other afferent such as propioceptive and visual system. </li></ul><ul><li>Central compensation initiated and enhanced by head movements- adaptation exercises and vestibular habituation therapy </li></ul>.

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Vastibular Rehabilitation <ul><li>General Principles </li></ul><ul><li>Decrease centrally sedating or vestibular suppressant drugs </li></ul><ul><li>Exercise must provoke vertigo </li></ul><ul><li>Initiate as early as possible </li></ul><ul><li>Exercise should simulate real life situations </li></ul><ul><li>Maintenance exercises to recurrence of symptoms </li></ul>

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Vertigo <ul><li>Agents affecting Vestibular Compensation- </li></ul><ul><li>Delayed Compes.- Barbiturates </li></ul><ul><li>Benzodiazepines </li></ul><ul><li>Antihistamines </li></ul><ul><li>Neuroleptics </li></ul><ul><li>Accelerated compes.- Betahistines </li></ul><ul><li>Flunarizine </li></ul><ul><li>Ginkgo-biloba extract </li></ul><ul><li>Caffeine </li></ul>

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Vertigo-Pharmacological Treatment <ul><li>Anticholinergics- </li></ul><ul><li>Homatropine and Scopolamine(Hyoscine) </li></ul><ul><li>First drug to be used in Vertigo </li></ul><ul><li>Non selective blocking all muscarinic receptor </li></ul><ul><li>subtypes(m1 to m5) </li></ul><ul><li>Adverse effects-Dry mouth, visual disturbences, </li></ul><ul><li>constipation, memory disturbances </li></ul><ul><li>cofusion, dysurea, glaucoma </li></ul>

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Vertigo-Pharmacological Treatment <ul><li>Antihistamines- </li></ul><ul><li>H1 Blockers </li></ul><ul><li>Mechanism- Poorly understand </li></ul><ul><li>? Antimuscaranic properties </li></ul><ul><li>Cinnarizine and flunarizine-Ca channel blockers </li></ul><ul><li>with significant H1 blocking effect </li></ul><ul><li>H2 blockers- Not used </li></ul><ul><li>Side effects- Sedation </li></ul><ul><li>Duration of action- 4 to 12 hrs. </li></ul>

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Vertigo-Pharmacological Treatment Histaminergic Medication- Betahistine

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Mode of action Betahistine Vascular Effects (in inner ear & brain) Neurological Effect (in brain)

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Betahistine-Vascular Effects H3 autoreceptor Antagonist Inhibits autoregulation of histamine release Improve cochlear micro circulation Improve cerebral/vertibrobasilar blood flow H1 Agonist

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Betahistine-Neurological Effects Regulates firing activity of Vestibular Nuclei Blocks H3 Receptors

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Betahistine : Pharmacokinetics <ul><li>Oral administration </li></ul><ul><li>Rapid and complete absorption </li></ul><ul><li>Mean plasma half-life : 3 to 4 hrs </li></ul><ul><li>Complete excretion via urine in 24 hrs </li></ul><ul><li>Very low plasma protein binding </li></ul><ul><li>2 inactive metabolites namely – Pyridylacetic acid </li></ul><ul><li>& 2-(2-aminoethyl) pyridine have been found </li></ul>

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Betahistine : Tolerability <ul><li>minimal side effects </li></ul><ul><li>No sedation </li></ul><ul><li>Low level of gastric side effects </li></ul><ul><li>No anticholinergic effcts </li></ul><ul><li>No extrapyrimidal side effects </li></ul>

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Betahistine : Contraindication <ul><li>Hypersensitivity to Betahistine </li></ul><ul><li>Pheochromocytoma </li></ul>

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Betahistine : Special Precautions <ul><li>Use with antihistamines </li></ul><ul><li>Patients with bronchial asthma </li></ul><ul><li>Patients with peptic ulcers </li></ul>

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Vertigo-Pharmacologic treatment <ul><li>Acetylleucine </li></ul><ul><li>Mechanisms </li></ul><ul><li>-? Precursors of neuromediator- peptidic- </li></ul><ul><li>Activation of vestibular afferent </li></ul><ul><li>-? Anti calcium properties </li></ul><ul><li>May enhance compensation </li></ul><ul><li>IV / Oral </li></ul>

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Vertigo-Pharmacologic treatment <ul><li>Antidopaminergic Drug </li></ul><ul><li>Block dopaminergic receptors in area postrema of the brainstem,has anticholinergic and antihistaminic(H1) activity </li></ul><ul><li>Neuroleptics neurovegetative symptoms </li></ul><ul><li>psychoeffective symptoms </li></ul><ul><li>- Phenothiazine derivatives </li></ul><ul><li>- Butyrophenones </li></ul><ul><li>- Benzamides </li></ul><ul><li>Domperidone & Metochlopramide </li></ul><ul><li>Adverse effects- Ortho.hypotension, </li></ul><ul><li>Somnolence,Extrapyramidal syndrome, </li></ul><ul><li>anticholinergic side effects; NMS </li></ul>

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Vertigo-Pharmacologic treatment <ul><li>Benzodiazepines </li></ul><ul><li>GABA modulators – act centrally to suppress vestibular response </li></ul><ul><li>May impair vestibular compensation </li></ul><ul><li>Anxiolytic effect </li></ul>

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Vertigo-Pharmacologic treatment Calcium Antagonist Adverse effects : Short term-Sedation,Weight gain Long term-Depression,Parkinsonism Cinnaizine(1966) Flunarizine(1985) Mechanism ? Vestibular hair cells endowed with ca channels - H1 antihistamnic properties -Sedative -Antidoaminergic action

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Vertigo-Pharmacologic treatment <ul><li>Miscellaneous </li></ul><ul><li>Ginkgo biloba </li></ul><ul><li>Piribidil- Dopaminergic agent </li></ul><ul><li>Ondansatron 5 HT3 antagonist </li></ul>

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To treat Vertigo A Physician needs a drug which……. <ul><li>Has Effect on cochlear & cerebral blood flow </li></ul><ul><li>Regulates vestibular nuclei firing </li></ul><ul><li>Offers symptomatic & prophylactic therapy </li></ul><ul><li>Does not interfere with compensation mechanism </li></ul><ul><li>Does not cause drowsiness </li></ul>

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Vertigo-Pharmacologic treatment <ul><li>Worldwide trends- </li></ul><ul><li>US – Benzodiazepines </li></ul><ul><li>Meclizine </li></ul><ul><li>France – Acetylleucine </li></ul><ul><li>Flunarazine </li></ul><ul><li>India - Cinnarizine </li></ul><ul><li>Betahistine </li></ul>

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Vertigo- Treatment <ul><li>General Comments </li></ul><ul><li>It is difficult to set out rational & well documented rules for administration of drugs. </li></ul><ul><li>Clinical pharmacology of anti vertigo drugs complex. </li></ul><ul><li>Clinical trials reliability? </li></ul><ul><li>Spontaneous recovery-Placebo control trials </li></ul>

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When to refer a Specialist <ul><li>Serious vertigo which is disabling </li></ul><ul><li>Vertigo lasting longer then 4 weeks </li></ul><ul><li>Hearing loss </li></ul><ul><li>CNS or psychological disorder </li></ul>

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Vertigo- Treatment <ul><li>General Guidelines </li></ul><ul><li>Acute disabling vertigo should be treated </li></ul><ul><li>Mild vertigo may be left alone </li></ul><ul><li>“ Omnious” vertigo should be investigated </li></ul><ul><li>Treatment period should be shortest possible </li></ul><ul><li>Lengthy confusing prescriptions should be avoided </li></ul><ul><li>Vestibular rehabilitation should be used early </li></ul>

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Vertigo <ul><li>Concluding Remarks- </li></ul><ul><li>Our habits of ant vertigo prescription are empirical and insufficiently evaluated </li></ul><ul><li>Improvement in practice of clinical pharmacology for vertigo is needed </li></ul><ul><li>New treatment may emerge from research in receptor subtypes, neuromodulators and agents affecting central compensation. </li></ul><ul><li>Vestibular rehab. Is underutilized </li></ul>

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Thanks