Disorder of Hypothalamus

Diseases of hypothalamus

1. HYPOTHALAMUS AND ITS CONNECTIONS (APPLIED) Dr. ATM HASIBUL HASAN MD (Neurology) Thesis Part Student Dhaka Medical College

2. Who should deal? Endocrinologist Neurologist

3. Alexis

4. Contents Imaging of Hypothalamus Diseases of Hypothalamus Presentation of Hypothalamic disease Dysfunction Hypofunction Hyperfunction Mechanical effect Brief description of some relevant diseases

5. About Hypothalamus O nly 0.3% of total brain, but is essential for life L ies in the centre of the limbic system C ontroller of body homeostasis D isorders may be global or partial

6. Nucleus Zone(s ) Region(s ) Functions Paraventricular Periventricular, Medial Anterior,Tuberal Fluid balance, milk let-down, parturition, autonomic & anterior pituitary control Preoptic Medial, Lateral Anterior Control parasympathetic system, thermoregulation , sexual behavior Anterior Medial Anterior Control parasympathetic sysrem, thermoregulation , sexual behavior Suprachiasmatic Medial Anterior Biological rhythms Supraoptic Medial, Lateral Anterior Fluid balance, milk let-down, parturition Dorsomedial Medial Tuberal Emotion (rage) Ventromedial Medial Tuberal Appetite, body weight, insulin regulation Arcuate Periventricular, Medial Tuberal Control of anterior pituitary, feeding Posterior Medial Posterior Thermoregulation Mammillary Medial Posterior Emotion and short-term memory Lateral Complex Lateral Tuberal Appetite and body weight control

7. Imaging of Hypothalamus Magnetic Resonance Imaging (MRI) Magnetization Transfer Imaging (MTI) Diffusion Weighted Imaging (DWI) Proton MR Spectroscopy 18 FDG PET SPECT Intraoperative Real Time Ultrasonography

8. MRI

9. Optic chiasm Median eminence Mamillary bodies

10. MTI

11. fMRI

12. When to Suspect ? Any feature of Diencephalic syndrome (FTT, vomiting and emaciation-Anterior hypothalamus) Precocious puberty (Tuber cinereum ) Hormone deficinecy Features suggesting mass effect on Chiasma Epilepsy: Gelastic seizure * Destructive lesion of hypothalamus never causes precocious puberty

13. Diseases Developmental disorders Midline cleft defects Kallman’s syndrome Septo -optic dysplasia Infiltrative and inflammatory diseases Sarcoidosis Tuberculosis Langerhans cell histiocytosis Encephalitis

14. C ont Space occupying lesions Craniopharyngioma Glioma Meningioma Hemangioblastoma Hamartoma Cysts : Epidermoid , dermoid , colloid Metastasis Lymphoma and leukaemia

15. C ont. Vascular Stroke Arterio -venous malformation Aneurysm Functional abnormalities Isolated hormone or receptor defect Systemic illness and psychosocial deprivation

16. C ont Iatrogenic Parasellar surgery Cranial irradiation Miscelleneous Hydrocephalus Pituitary adenoma Wernicke’s encephalopathy

17. Effects Dysfunction Endocrine Autonomic regulation Temperature regulation Eating behavior Mechanical effects Optic chiasma compression Hydrocephalus

18. Endocrine dysfunctions Hypofunctions Growth hormone deficiency Hypothalamic hypogonadism Secondary hypothyroidism Central diabetes insipidus Pituitary insufficiency

19. Cont . Hyperfunctions Hypothalamic precocious puberty Hypothalamic hyperprolactinaemia Syndrome of inappropriate ADH secretion

20. Abnormalities of Growth: ( Def /Excess of GHRH/GH) Dwarfism Acromegaly Gigantism

21. Cont. Causes of GH Deficiency: Idiopathic / functional Congenital idiopathic growth hormone deficiency Emotional deprivation syndrome GH deficiency in chronic illness Hypothalamic gangliocytomas Pituitary tumor * GH deficiency due to hypothalamic disorder are mostly functional

22. C ont. Hypothalamic hypogonadism Causes Isolated GnRH deficiency Structural lesion of hypothalamus Hyperprolactinaemia

23. A 3yr old girl presented with regular monthly PV bleeding for last 6 months. Her parents also noticed brief spells of abnormal laughter for last few months. Hypothalamic Hamartoma

24. C ont. Hypothalamic hypergonadism Causes- Structural lesion of hypothalamus ( Hamartoma most common) Idiopathic More common in females (most are idiopathic) Males are more severely affected (most are structural lesions)

25. Precocious Puberty Abnormally early onset of androgen secretion in boys (<9yrs) and estrogen secretion in girls (<8yrs). Causes- Teratoma of pineal gland or mediastinum, androgenic tumour of testes and adrenal- male Hypothalamic disease and estrogen secreting ovarian tumours -female Hamartoma in both sexes, in a number of cases gelastic seizure have been conjoined. Treatment: GnRH analogue: Leuprolide

26. A 32yr old man presented with intermittent fever, cough, breathlessness, polyuria and polydipsia Cranial Diabetes Insipidus due to Sarcoidosis

27. Cranial diabetes insipidus Pathogenesis Lack of ADH Impaired renal water reabsorption Diuresis Raised plasma osmolarity Increased thirst

28. Cranial diabetes insipidus Cause Parasellar surgery Head injury ICSOL Infiltrative granulomatous disease eg . Neurosarcoidosis Congenital eg . Wolfram syndrome (DIDMOD) Drugs eg.CBZ, lithium Idiopathic

29. CDI Investigation Water deprivation test : Plasma osmolality > 300 mOsm /L Urine osmolality < 600 mOsm /L > 50% improvement after administration of DDAVP RIA of plasma ADH: usually <1.0 pg/ml (n=1.4-2.7 pg/ml)

30. A 66 yrs old man presented to ER with headache, confusion and unsteadiness. He had H/O PTB 15 yrs back. On query the attendants also reported frequent cough with sputum production for last 6 yrs. SIADH due to Bronchiactasis

31. Syndrome of inappropraite ADH secretion (SIADH) Pathogenesis : Excessive ADH Excessive water reabsorption in collecting tubule Dilutional hyponatraemia

32. SIADH Causes- CNS disorders :Stroke, infection, injury, tumor Pulmonary disorders : Pneumonia, TB , CA Drugs : Carbamazepine, TCA, Antipsychotic Ectopic production of ADH : Carcinoma, thymoma , mesothelioma, lymphoma Idiopathic

33. SIADH Diagnosis Low plasma sodium (<130 mmol /L) Low plasma osmolality (<270 mosmol /L) Urine osmolality not minimally low (> 150 mosmol /L) Urine Na not minimally low (>30 mmol /L) Exclusion of other causes Appropriate clinical setting

34. A 42 yrs old alcoholic man presented to ER with sudden fall and unconsciousness. The situation was further complicated by alcohol withdrawal seizure. After initial improvement patient again developed confusion at 10 th day and there was postural drop of BP. Investigation revealed nothing but hyponatremia (Na level is 122 mmol /l). Cerebral Salt Wasting Syndrome

35. Cerebral Salt Wasting Syndrome Also known as Neurogenic SWS Caused by – A cute intracranial diseases, Tumor Post neurosurgical procedure Pathophysiology- Decreased sympathetic drive BNP and ANP Effect- Sodium loss rather than water retention Fluid restriction may be dangerous Opposes the action of ADH in RT and also inhibit ADH release from hypothalamus

36. SIADH & CSWS Features Common: Hyponatremia Urine osmolality: Increased Urine Na: >20 mEq /L Urine osmolality > serum osmolality Often similar clinical context

37. Distinguishing features between SIADH & CSWS

38. Disturbance of temperature regulation Hyperthermia : Anterior hypothalamic lesion ( Preoptic ) Hypothermia : Posterior hypothalamic lesion Persistent temparature of ≤ 35°C (95°F) Poikilothermia : Large lesion in the posterior hypothalamus

39. Disturbance of temperature regulation Causes: Structural – stroke, head injury, surgery, demyelination Functional – Spontaneous recurrent hypothermia Shapiro’s syndrome ( cholesteatoma of 3 rd V.) Reverse Shapiro’s syndrome

40. Disturbance of Autonomic regulation Acute autonomic crises ( Sympathetic storm ) An exacerbation of stress response Causes- Toxic and pharmacologic agents- Cocaine Phenylpropanolamine TCA overdose OP insectisides Severe head injury Hypertensive ICH

41. Disturbance of Autonomic regulation Presentatoin - Abrupt overactivity of sympathetic and parasympathetic nervous system Occcasional sign of CNS excitation eg . seizure Cushing response/reflex (HTN, ↓ HR, Irreg. RR) Diencephalic seizure (Paroxysmal HTN, intense diaphoresis, flushed skin and mydriasis )

42. Disturbance of body weight Hypothalamic obesity : Lesion in Ventromedial hypothalamus Paraventricular nucleus Effect- Uncontrolled voracious appetite causing the pt extreme obesity

43. Disturbance of body weight Hypothalamic weight loss : Lesion in Lateral hypothalamus Dorsomedial nucleus May be associated with Hypothalamic tumour or disorder of behavior (Anorexia Nervosa) Adolescent girls are affected

44. Periodic somnolence and bulimia Known as Kleine -Levin Syndrome Hypothalamus is responsible, but without definite pathologic confirmation Usually adolescent boys are affected Episodic disorder characterized by somnolence and over eating Pt. sleep ≥18 hrs/day, waking only to eat and attend to toilet needs They appeared dull, often confused and restless

45. Developmental disorders Midline cleft syndromes : Developmental abnormalities of Skull and brain with Hypopituitarism (varying degree)

46. C ont. Septo -optic dysplasia: Agenesis of septum pellucidum Hypoplastic optic nerve Hypothalamic precocious puberty

47. MRI showing absent septum pellucidum with characteristic configuration of frontal horns. V ery thin optic chiasm. Thin corpus callosum and low fornices . Pituitary has normal appearance. Septo optic Dysplasia/ De Morsier Syndrome

48. Kallman’s syndrome: X-linked recessive Clinical features Hypogonadism Anosmia Tall stature Mental retardation , Deafness , colour blindness Absent secondary sexual characteristics Kallman’s syndrome Normal

49. Developmental disorders (cont.) Investigation Low GnRH , LH, FSH, testosterone MRI : Hypoplastic or absent olfactory bulbs MRI through frontal lobe showing absent olfactory bulb

50. Rathke Cleft Cyst Benign sellar cyst Derived from Rathke Pouch remnant Presents in 5 th -6 th decade Features of compression of pituitary or hypothalamus

51. Craniopharyngioma Origin : Remnants of Rathke’s pouch ( Craniopharyngeal duct) Types : Adamantinoma (Children) Papillary (Adult) Presentation: Raised ICP Visual field defect Hypopituitarism, commonly DI

52. 8 yr old boy - Adamantinoma 39 yr old man Papillary CP

53. Hypothalamic Chiasmatic Glioma About 10-15% of supratentorial tumor in children Presents at 2-4 yrs of age D iminished visual acuity Short stature ( GH ) F/H/O NF-1 Slowly progressive with occasional spontaneous remission

54. Haemangioblastoma are benign vascular tumor (2%) Usually 35-45 yrs of age Rarely affects hypothalamus- mostly Von Hippel Lindau Hemangioblastoma

55. Encephalitis Mostly viral Presents with fever, Central DI, SIADH

56. A 61-year-old woman developed a rapidly progressive dementia associated with visual loss. In 7 mo she was dependent for self-care. Coronal T2-weighted [A], axial FLAIR [B], and axial contrast-enhanced T1-weighted images [C and D] demonstrate extensive involvement of the hypothalamic and suprasellar regions, extending laterally towards the optic tracts, and to the left temporal lobe. The enhancing portion of the lesion is hypothalamic and suprasellar , and there is also a component of enhancement in the anterior portion of the temporal lobe (arrow in D). Neurosarcoidosis involving Hypothalamus

57. Neurosarcoidosis Neurosarcoidosis occurs in approximately 5% cases of all sarcoidosis . Presentation: Aseptic meningitis Cranial nerve palsy Hypothalamic dysfunction : DI Tumor like effect: seizure, hemiparesis

58. Neurosarcoidosis (cont.) Investigations Chest X-ray Histopathology/cytology Serum calcium Serum ACE CSF study (including ACE level) MRI brain

59. Neurosarcoidosis (cont.) Treatment: Corticosteroid Cyclosporin Cyclophsphamide Radiation of focal lesion