1. Department of Psychiatry K. J. Somaiya Medical College and Research Centre, Mumbai

5. Vascular Infective Epilepsy Toxin Neoplasm Auto – Immune Metabolic Deficiency Idiopathic Endocrine Trauma

7. CASE 1 DR. SHUBHANGI S. DERE

8. Mr. S, 31 years old, rt handed, married Muslim male, studied upto 9 th std, currently not working, residing at Kurla, brought by mother, with c/o: - Withdrawn behavior - Sadness of mood - Ideas of H/H - Slowness of movements - Poor sleep …. Since 1 year Gradual onset of above symptoms due to which patient stopped working

9. Shown to private psychiatrist treated with medicines & 5 ECTs (details of medicines not available) Rx stopped as no improvement perceived. Shown at psychiatry dept in municipal hospital, diagnosed as MDD, started on T. Nortryptyline (25mg) 1-1-2 T. Mirtazepine (30mg) 0-0-1 T. Bupropion SR (150mg) 0-0-1 T. Alprazolam (1mg) 1-0-1 10 ECTs given. Perceived no improvement even with 2 months of regular Rx On f/u: increased withdrawn behavior, crying spells, forgetfulness, hence discontinued Rx.

10. Referred to K. J. S. H. in Oct. 2012 C/o- Withdrawn behavior - Sadness of mood, Ideas of H/H - Slowness of movements - Poor sleep - One episode of self harming behavior On enquiry, h/o tremulousness, slurring of speech & leaning of body backwards while sitting ….since few months No h/s/o manic, psychotic features or substance use No significant past/ family history Birth, developmental history- uneventful H/s/o marital disharmony + PMP- extrovert, non impulsive, well adjusted

11. On examination: GC- Fair, Vitals stable. No pallor/ icterus/ cyanosis/ lymphadenopathy B/l tremors +, course On Neurological examination: Speech- slow with gradual slurring Gait- normal Cranial nerves examination: WNL Motor system: Tone- WNL, Power- 5/5 Slow initiation of movements, Gradual deterioration of writing. DTR- Brisk No cerebellar signs No signs of meningeal irritation or raised ICT Other systemic examination: NAD

12. MENTAL STATUS EXAMINATION: Conscious, cooperative, communicative Psychomotor retardation + Grimacing facial movements, mannerisms + Attention- Arousable and sustained ETEC- Established Rapport- Established Mood- Sad Affect- Restricted

13. MENTAL STATUS EXAMINATION (contd..): Speech/ thought- C/C/R, low volume,slurred speech I/H/H, PDW Denies delusion Concepts- intact Denies perceptual abnormality Memory - Intact Oriented to T/P/P Judgment- Intact Insight- 4/6 MMSE: 30/30

14. On ROR:- Pt’s reality testing was intact with popular responses. - Responses indicated limited view of world with child like immaturity and anxiety. - No bizzare contents. Neurology reference done i/v/o tremors, dystonic posturing of back and slowness of movements. Advised MRI which showed gliosis with calcification in b/l basal ganglia s/o ? Wilson’s disease.

16. Ophthalmological examination: Keyser Fleischer ring +

17. On investigations: Hb- 13.6, CBC- 4800, DLC- WNL Platelet count- 83,000 ( ) LFT: SGOT- 98 ( ) SGPT- 139 ( ) Sr. bilirubin- WNL Alkanine phosphatase, serum proteins- WNL Serum Phosphorous, Mg, Ca- WNL Urine Cu- 48.30 ( ) (normal upto 40mcg/dl) 24 hour urine Cu- 72.45 ( ) (Range- 15-60mcg/day ) Lipoprotein electrophoresis- WNL Sr. PTH, T3, T4, TSH, Vit D3, Vit B12- WNL Patient was diagnosed with Wilson’s disease.

18. WILSON’S DISEASE

19. Autosomal recessive disorder Muliple mutation of gene ATP7B on chromosome 13q14.3 (critical for hepatic Cu excretion) Cu deposition primarily in liver and basal ganglia Brain pathology: Gliosis, astrocyte proliferation, spongy necrosis, demylination, denervation Diagnosis: High urinary Cu levels (>40 mcg/dl) KFR Decreased blood ceruloplasmin levels Increased Cu levels on liver biopsy (> 150mcg/gm)

20. Neurological signs: Subtle. Most common: Tremors, speech difficulties, micrographia A study by Huang C. C. et al: 73.2% presented with neurological signs at time of diagnosis Tremors (66.2%) Dysarthria (56.3%) Gait disturbances (46.5%) Generalised multifocal dystonia (42.3%) Decreased facial expression (40.8%) Rigidity (33.8%) Increased deep tendon reflexes (23.9%)

21. Psychiatric manifestations: 33% - predominant manifestation at onset 67% - present with neurological symptoms at outset Predominant psychiatric morbidity: Personality changes: In about 50%, i/f/o irritability, apathy, disinhibition causing marital disharmony Mood disorders: MDD in 30% Cognitive disturbances : Less than 25% Half of the patients undergo psychiatric hospitalization before WD is diagnosed Treatment: Cu chelating agents

23. CASE -2 DR. DIMPLE DADARWALA

24. Mr. M, 21 years old, right handed, Hindu, Hindi speaking, male, student of 2 nd year B.A., unmarried, hailing from U.P., brought by relatives to psychiatry O.P.D., with complaints of Altered behaviour i/f/o excessive, irrelevant talk irritability, anger outburst stubborn behaviour Since 1 month

25. 4 years back episode of tonic clonic movement of right upper extremity f/b loss of consciousness for 10-15 min. MRI - reports not available. Started on T. Phenytoin 100 mg, gradually increased to 300mg contd for 3 years. Stopped in Jan 2012 on doctor’s advice. July 2012 similar episode MRI - Left parietal lobe ring enhancing lesion Neurocysticercosis(NCC) Restarted T. Phenytoin 100 mg increased to 100 mg TDS T. Levetiracetam 500mg BD added T. Albendazole 200 mg BD was given for a week

26. 2 months back had giddiness, swaying, loss of balance and h/o two falls - left side of body and on back Since 1 month altered behavior i/f/o excessive, irrelevant talk talking with increased gestures and blinking of eyes irritability on minimal provocation anger outburst during conversation Brought to KJSH psychiatry O.P.D.

27. No h/o disorganised / disinhibited / catatonic features/ suspiciousness/ hearing voices inaudible to others No h/s/o Mania/ OCD/ Depression/ Anxiety/ DSH/ Substance use Past History : No h/s/o medical / surgical / psychiatric illness Family History : No family h/s/o psychiatric illness Personal History : FTND milestones normally achieved 2 nd year B.A. student unmarried

28. On General Examination: General Condition : fair Vitals stable Gum hypertrophy + Pallor + No icterus / clubbing/ lymphadenopathy / edema Scar on left cheek

29. On CNS Examination: Higher functions : discussed in MSE Motor Examination- Tone : normal Power : 5/5 Sensory Examination : normal Cranial Nerves Examination : normal Reflexes : DTR 2+, Planters Cerebellar Signs : Tandem walk +, Rhomberg sign +, No other cerebellar signs

30. On Mental Status Examination: Pt talks with increased gestures Conscious/ cooperative/ communicative ETEC : I/m Attention : A/IS Rapport : established easily Mood : happy Affect : congruent

31. Speech /Thought : C/C/ occ irrelevant, pressure of speech, tangentiality denies delusions, i/o h/h/w Concepts : impaired Perceptions : denies any perceptual abnormality Oriented to t/p/p Memory : not possible Judgment : impaired Insight : 1/6

32. Provisional Diagnosis: Behavioural Changes due to : Phenytoin Toxicity Interictal Behavioural changes Neurocysticercosis

33. Patient admitted and started on T. Olanzapine 2.5 mg HS BG Test: Presence of organicity

34. ROR Test : - Pt’s reality testing was not intact - Perplexity and impotency of responses - Fine details and pickiness was observed - S/o organicity. Neurology opinion taken i/v/o cerebellar signs Advised S. Phenytoin levels, EEG, MRI S. Phenytoin - 36.70mcg/ml ( normal 10-20mcg/ml) EEG –normal MRI – near resolving NCC Final diagnosis: Phenytoin Toxicity

35. T. Phenytoin tapered and stopped over 10 days Pt discharged on T. Levetiracetam 500mg BD T. Olanzapine 2.5mg HS On Follow Up: Pt had near total improvement in psychiatric symptoms No h/o giddiness, swaying, loss of balance, fall, seizure episode MSE : unremarkable T. Olanzapine 2.5 mg tapered and stopped over 20 days. T. Levetiracetam 750 mg contd

36. PHENYTOIN TOXICITY  The therapeutic range is 10-20 mcg/ml.  Phenytoin metabolism is dose dependent.  Elimination follows first-order kinetics at low drug conc and zero-order kinetics at higher drug conc.  Significant elevation of Phenytoin conc to toxic level can result from addition of Levetiracetam to Phenytoin in rare instances.  Plasma levels (mcg/ml) have an association with acute neurological symptoms and clinical evidence of toxicity.

37.  Neurological symptoms Lower than 10 : Rare * 10 - 20 : Occasional mild nystagmus * 20 - 30 : Nystagmus * 30 - 40 : Ataxia, slurred speech, nausea, and vomiting * 40 - 50 : Lethargy and confusion * Higher than 50 : Coma and seizures Possible psychiatric symptoms: * mood or behaviour changes * depression and anxiety * agitation, hostility, restlessness * hyperactivity (mentally or physically) * suicidal ideation

38. Phenytoin intoxication should be considered when any unusual neurological or behavioural disturbance occurs in a patient receiving phenytoin. A similar case report published in IJP July –September 2012.

40. CASE 3 Dr Adita Dagaria

41. Miss N, 16 years, female, Right handed, Muslim, Hindi speaking, in 10 th standard, brought by parents with following complaints: 1 episode of GTC …….. 2 months back Episodes of ghabrahat, palpitations, breathlessness, feeling of impending doom and unresponsiveness, followed by fearfulness 1 1/2 Sadness of mood, decreased interest in talking months to others, irritability

42. HISTORY OF PRESENTING ILLNESS Patient was apparently alright 2 months back when she had 1 episode of involuntary movements of limbs, uprolling of eyeballs, frothing from mouth, tongue bite, incontinence of urine. This lasted for about 5-10 minutes. She was unresponsive for 2-3 hours and did not have recall of the episode. Was started on T. Phenytoin from private hospital. CT Scan Brain - normal.

43. After 10-15 days, started having episodes of ghabrahat, palpitations, breathlessness, feeling of impending doom and unresponsiveness for 10-15 minutes. This was followed by fearfulness because of which she used to sit in a corner, if anyone tried to come near her she used to become aggressive and abusive. Initially these episodes used to be once in 2-3 days but after 10-12 days, frequency of episodes increased, with same pattern of episodes.

44. Also, she started having sadness of mood, withdrawn behaviour, ideas of H/H/W and feelings of guilt. For this, patient was shown in a municipal hospital and was diagnosed as Panic disorder. EEG – Normal. Was started on T. Paroxetine (12.5 mg) twice a day T. Clonazepam (0.25 mg) SOS. However no improvement was perceived and therefore she was brought to K.J.Somaiya Hospital.

45. No h/o catatonic/ disorganized/ disinhibited behaviour, mania, OCD, substance use. No h/o anger outbursts, temper tantrums, head banging, nail biting, bedwetting, conduct problems. No history of any other major medical and surgical illness. Family H/o – 1 st among 5 siblings. No family h/o psychiatric illness and epilepsy.

46. Personal H/o – FTN, home delivery milestones achieved normally in 10 th standard good in studies financial stressor + no sibling rivalry unmarried menses regular Temperament – anxious, well adjusted socially

47. General examination : GC – fair Vitals - stable No pallor, icterus, cyanosis, clubbing, lymphadenopathy Systemic Examination – NAD

48. Mental Status Examination: Conscious, cooperative, communicative Attention: Arousable and sustained Rapport- established Mood- worried Affect- appropriate

49. Thought/Speech- C/C/R I/o H/H/W Denies delusions/ SI Concepts: Intact No perceptual abnormality Oriented to T/P/P Memory: Intact Judgement: Intact Insight: 4/6

50. TAT : Pt stories were well narrated and described. Pt identified with victim character facing life problems. Pt projected financial stressor and very high self expectation on the stories. Anxiety regarding future and helplessness was observed. Patient had strong super ego

51. Diagnosed as MDD with ?Conversion disorder, ?Panic disorder Pt was admitted & continued on T. Paroxetine (12.5 mg) BID T. Clonazepam (0.25 mg) BID No improvement was perceived in the episodes. Neurology reference was done EEG done- generalized spike and sharp wave were seen.

52. Diagnosis was revised to seizure disorder and patient was started on T. Carbamazepine. Dose of T. Paroxetine was reduced to 12.5 mg. After this, frequency of episodes decreased and patient perceived near total improvement. MSE was unremarkable. Patient lost to follow up.

53. SIMPLE PARTIAL SEIZURES Preserved consciousness Sudden and inexplicable feelings of fear, anger, sadness, happiness or nausea Sensations of falling or movement Experiencing of unusual feelings or sensations Sensory illusion or hallucinations, derealization, depersonalization Déjà vu (familiarity) or jamais vu (unfamiliarity) Laboured speech or inability to speak at all Usually the event is remembered in detail

54. PSYCHIATRIC MORBIDITY A study done by Vuilleumier & Jallon estimated that 20-30% of patients with epilepsy have psychiatric disturbances. The most common psychiatric conditions are depression, anxiety, and psychoses. Torta and Keller reported that the risk of psychosis may be 6-12 times that of the general population, with a prevalence of about 7-8%.

55. PSYCHIATRIC MANIFESTATIONS PSYCHIATRIC DIAGNOSISPATIENTS WITH EPILEPSY MDD17.4% ANXIETY22.8% MOOD/ANXIETY DISORDER34.2% SUICIDE25% OTHERS35.5%

57. CASE : 4 DR. KEDAR TILWE

58. Ms. A 2O yrs, female, right handed, Hindi speaking, Muslim, studied till 7 th std, unmarried, resident of Uran, brought by mother with c / o - Episodes of uneasy sensation in abdomen with nausea, retching & unresponsiveness …. 3 months - Difficulty in naming relatives …. 2 months Patient is a k/c/o epilepsy on treatment since 6 months

59. 3 episodes of convulsions 6 months back. Started on T. Phenytoin …. discontinued after 1 month Seizures increased over next month (2 /day) …hospitalized. In hospital ; irritable, abusive, running around & pulling her hair … diagnosed as Post ictal psychosis - E.E.G. was normal - CT Brain : Right temporal lesion s/o calcified granuloma - Advice on discharge : T. Phenytoin 100mg OD T. Phenobarbitone 30mg OD T. Carbamezapine 400mg BID T. Librium 10mg TDS

60. Patient started c/o episodic feeling of uneasiness in abdomen followed by nausea, retching and period of unresponsiveness ; which gradually worsened along with severe right sided headache Seizures also continued. Suddenly 2 months back patient started calling her mother - malishwali father - malik brothers - watchmen sisters - naukrani But could identify them on the basis of their peculiarities

61. MRI Brain: small calcified granuloma in right temporal area Readmitted for 15 days Discharged on T. Carbamezapine 400mg BID T. Chlordezpoxide 10mg TDS T. Clobazam 10mg BID T. Escitalopram 10mg OD However the episodes of naming difficulty & nausea persisted so brought to K.J.S.H. psychiatry opd 1 month later. Relatives also noted: irritable, withdrawn, stubborn & regressed behavior

62. No h/s/o psychosis / mania /depression/ OC features/ substance abuse Past history : 1 episode of convulsion in 6 th standard. No h/s/o other major medical/surgical illness Family history : No significant psychiatric Illness in family Personal history : F.T.N.D. at home – port wine stain detected Milestones achieved normally Studied till 7 th std PMP: Extrovert, well adjusted

63. General examination G.C. – Fair Vitals stable Pallor + Port wine stain on Left side of face, neck & hand No icterus/ cyanosis/ lymphadenopathy Systemic examination NAD

64. MENTAL STATUS EXAMINATION Conscious /cooperative/ communicative Over familiarity + Sitting comfortably but agitated when asked to identify people by name. Facial agnosia + Rapport : established Attention : arousable but ill sustained Eye to Eye contact : initiated & maintained Mood : Happy Affect : Appropriate

65. Speech : Normal Thought : C / C / R Circumstantiality Denied delusions Denied ideas of H/H/W Denied Perceptual abnormalities Oriented to T/P/P Memory : Intact Judgment : Impaired Insight : IV

66. EEG : Left sided neuronal hyper excitability ROR : Reality testing not intact Limited view of world Color naming & impulsivity observed No bizarre content BG : Absence of organicity

67. Medicine opinion : Scar epilepsy with anxiety Ophthalmology opinion : Normotensive glaucoma Dermatology opinion : Left sided port wine stain Neurological diagnosis : Sturge - Weber syndrome

68. Started on: T. Clobazam 5mg BID T. Clonazepam 0.25 mg OD T. Piracetam 800mg TDS C. Autrin OD On discharge: Patient better No over familiarity or agitation Had started identifying relatives MSE unremarkable

69. Sturge–Weber syndrome

70. Part of neurophakomatoses Incidence : 1 in 50,000 births Symptoms : Port wine stain Epilepsy Triad Glaucoma Neurological : Headaches,F.N.D. & Hemiatrophy C.T. / M.R.I may detect intracranial abnormalities Treatment : symptomatic – ( anti-epileptics, glaucoma management, cosmetic management of stain )

71. Psychiatric manifestations Mental retardation (higher if seizures onset < age of 1yr ) Associated with violence, aggression, self injurious behavior & learning disabilities Depression Other emotional problems – Anxiety, low self-esteem, shame, emotional outbursts & isolation Behavioral disturbances due to epilepsy

77. P ATIEN T