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
o Dysfunction
Hypofunction
Hyperfunction
o Mechanical effect
Brief description of some relevant diseases

5. About Hypothalamus
• Only 0.3% of total
brain, but is essential
for life
• Lies in the centre of
the limbic system
• Controller of body
homeostasis
• Disorders may be
global or partial

7. 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

9. 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

10. MRI

11. a. Optic chiasm
b. Median eminence
c. Mamillary bodies

12. MTI

13. fMRI

14. 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

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

16. Cont
 Space occupying lesions
 Craniopharyngioma
 Glioma
 Meningioma
 Hemangioblastoma
 Hamartoma
 Cysts : Epidermoid, dermoid, colloid
 Metastasis
 Lymphoma and leukaemia

17. Cont.
 Vascular
 Stroke
 Arterio-venous malformation
 Aneurysm
 Functional abnormalities
 Isolated hormone or receptor defect
 Systemic illness and psychosocial deprivation

18. Cont
 Iatrogenic
 Parasellar surgery
 Cranial irradiation
 Miscelleneous
 Hydrocephalus
 Pituitary adenoma
 Wernicke’s encephalopathy

19. Effects
Dysfunction
 Endocrine
 Autonomic regulation
 Temperature regulation
 Eating behavior
Mechanical effects
 Optic chiasma compression
 Hydrocephalus

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

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

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

23. 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

24. Cont.
Hypothalamic hypogonadism
Causes
 Isolated GnRH deficiency
 Structural lesion of hypothalamus
 Hyperprolactinaemia

25. 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

26. Cont.
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)

27. 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

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

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

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

31. 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)

32. 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

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

34. 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

35. 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

36. 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 10th day and there was postural
drop of BP. Investigation revealed nothing but hyponatremia (Na level is 122
mmol/l).
Cerebral Salt Wasting Syndrome

37. Cerebral Salt Wasting Syndrome
• Also known as Neurogenic SWS
• Caused by –
 Acute 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

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

39. Distinguishing features between SIADH & CSWS

41. 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

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

43. 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

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

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

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

47. 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

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

49. Cont.
Septo-optic dysplasia:
• Agenesis of septum pellucidum
• Hypoplastic optic nerve
• Hypothalamic precocious puberty

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

51. 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

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

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

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

56. 8 yr old boy - Adamantinoma 39 yr old man Papillary CP

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

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

60. Encephalitis
• Mostly viral
• Presents with fever,
Central DI, SIADH

61. 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

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

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

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

65. Hypothalamus
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