Cerebellar disorders

Cerebellar disorders

1. CEREBELLAR DISORDERS STUDENT : DR MEDINI S GUIDE : DR SACHIN HOSAKATTI

2. HEADINGS ANATOMY CONNECTIONS FUNCTIONS DISTURBANCES

3. ANATOMY INTRODUCTION CEREBELLUM (LATIN) – little brain Weight = 150 gm Location – posterior cranial fossa

4. Situated in the posterior cranial fossa & covered superiorly by the tentorium cerebelli. largest part of the hindbrain (10% of total wt ) and lies posterior to the 4 th ventricle, the pons, and the medulla . It consists of two cerebellar hemispheres joined by a narrow median vermis.

5. It has t hree symmetrical bundles of nerve fibers called the superior, middle, and inferior cerebellar peduncles. Superior peduncle connects with mid brain Middle peduncle connects with pons Inferior peduncle connect with medulla

6. The cerebellum is divided into three main lobes: the anterior lobe, the posterior lobe, and the flocculonodular lobe. The anterior lobe may be seen on the superior surface. It is separated from the posterior lobe by a wide V-shaped fissure called the primary fissure.

7. Three Parts- Cerebellar hemisp h ere s Appendicular coordination Vermis Connection between hemispheres Gait and axial function Flocculonodular lobe Paired lateral flocculi with midline nodulus Eye movements & balance Cerebellar tonsils- small, rounded lobules on inferior aspects of cerebellar hemispheres, just above the foramen magnum

8. PHYLOGENETIC DIVISIONS Floc c ul o no d ul a r Lobe ArchiCerebellum Anterior Lobe PaleoCerebellum Posterior Lobe N e o C erebellum Middle divisions of vermis and their lateral extensions.

9. ANATOMICAL SUBDIVISIONS OF CEREBELLUM V e s tibuloCe r ebellum SpinoCerebellum PontoCerebellum Ventral Spinocerebellar tract Dorsal Spinocerebellar tract

10. Same as the fl o c c u l o n o d u l ar lobe Proprioceptive fibers from the Vestibular nuclei Functions Eye movement Gross balance and orientation in space V estibulocerebellum

11. Flocculonodular Lobe Connections are to Afferent Labyrinths Vestibular centers Spinal cord Brainstem Reticular formation Olivary bodies Efferent Vestibular nuclei Vestibulospinal tract Reticular formation The manifestations are difficult to separate from invariably involved vestibular findings. Isolated FN lobe dysfunction is usually seen in children in- Ependymomas Medulloblastomas

12. Spino/Paleocerebellum (evolved when extremity control was not a concern) Anterior and part of Posterior Vermis (and paravermal cortex) Proprioceptive fibers from muscles and tendons of limbs Functions Influence posture, muscle tone, axial muscle control, locomotion Dorsal Spinocerebellar Tract from lower limbs Ventral Spinocerebellar tract from upper limbs

13. Paleocerebellum Afferent connections Anterior spinocerebellar tract Trigeminocerebellar fibers Input from vestibular nucleus Corticocerebellar fibers Efferent connections Vestibular nucleus Brainstem Spinal cord

14. Pontocerebellum Roughly the same as neocerebellum Afferent from pontine nucleus and brachium pontis Coordination of skilled movements initiated at cerebral cortical levels

15. Neocerebellum Afferent connections Cor t i c o p o n ti n e/ c o r ti c o p o n to c e r e b e l l ar fibers Spinocerebellar fibers (few) Efferent connections To red nucleus To thalamus To cerebral cortex via Dent a te Nucleus

16. Vermis - Divisions Sup part of vermis Lingula Culmen Declive Folium Inferior part of vermis Tuber Pyramid Uvula Nodule

17. CEREBELLUM

18. Structure of cerebellum Cerebellum is a composite of White matter core Grey matter thin cortex Cerebellar nuclei- deep grey matter structures Nuclei Dentate nucleus Emboliform nucleus N ucleus Globose nucleus interpositus Fastigial nucleus

19. Cerebellar Cortex 3 Layers: Granular Purkinje Molecular 5 Cell types: Basket, stellate, Purkinje, granule, and Golgi

20. PHYSIOLOGY Ascending Fibres: Mossy Diffuse projections through granule cells to multiple Purkinje cells Climbing Terminal fibers of olivocerebellar tracts, multiple synaptic contacts per Purkinje cell

21. PHYSIOLOGY Descending Fibres: Purkinje Fibres Project from Purkinje cells in Purkinje layer to deep cerebellar nuclei, inhibitory Deep nuclei then send excitatory signals to their efferent connections

22. DEEP NUCLEI OF CEREBELLUM Dentate nucleus Emboliform nucleus Globus nucleus Fastigial nucleus

23. Functional Anatomy Organized into Midline, Intermediate and lateral zones Midline - project to fastigial nuclei Intermediate - project to nucleus interposed Lateral - project to dentate

24. Therefore, motor control of the cerebellum is by connection with Motor cortex Brainstem nuclei Descending motor pathways

25. Functions of Deep Nuclei Dentate Nucleus Fastigial Nucleus Receives fibers from- Premotor cortex. Supplementary motor cortex. Initiate volitional movements. Inactivation of dentate nucleus - delayed initiation of such movement. Controls antigravity muscles and other muscle synergies in standing and walking.

26. Nuclei Interpositus Cerebrocortical projections via pontocerebellar system. S p i n ocerebellar projections Information from Golgi tendon organs, muscle spindles, cutaneous afferents, subcutaneous interneurons. Fires when movement has started. Dampens physiological tremors- Intention tremors if interrupted

27. Blood supply Posterior inferior cerebellar artery Anterior inferior cerebellar artery Branch of basilar artery Superior cerebellar artery

28. Vascular Supply PICA From intracranial vertebral artery, supplies the lateral medullary tegmentum, inferior cerebellar peduncle, the ipsilateral portion of the inferior vermis, and the inferior surface of the cerebellar hemisphere AICA above the origin of the basilar artery, supplies the anterior petrosal surface of the cerebellar hemisphere, flocculus , lower portion of the middle cerebellar peduncle, and lateral pontomedullary tegmentum SCA distal segment of the basilar artery just below the terminal bifurcation into the paired PCAs, and supplies the upper surface of the cerebellar hemisphere, ipsilateral portion of the superior vermis , most of the dentate nucleus, upper portion of the middle cerebellar peduncle, superior cerebellar peduncle, and lateral pontine tegmentum

29. CE R EB E L L AR PEDUNCLES

30. Superior Cerebellar Peduncle Brachium Con j u n c t i v um Principally efferent Chief efferent fibres Dentatorubral Dentatothalamic Also Anterior spi n ocerebe l lar C e rebe l l o vestib u l a r tract

31. Afferent fibres include The ventral spinocerebellar tract transmits proprioceptive and exteroceptive information from levels below the midthoracic cord. The tectocerebellar tract, arising in the superior and inferior colliculi carries auditory and visual information. The trigeminocerebellar tract carries proprioceptive fibers from the mesencephalon and tactile information from the chief sensory nucleus of the trigeminal nerve. The cerulocerebellar tract carries fibers from the nucleus ceruleus.

32. Efferent fibers include The dentatorubral tract carries output to the contralateral red nucleus. Many of the fibers ending in this nucleus are branches of the larger dentatothalamic tract. The dentatothalamic tract transmits output to the contralateral ventrolateral nucleus of the thalamus.

33. Middle Cerebellar Peduncle Brachium Pontis Greatest peduncle Traversed by po n to c er e be l lar tracts Connects cerebral cortices to C/L cerebellar hemisphere

34. Pontocerebellar (corticopontocerebellar) tract arises in the contralateral pontine gray matter and transmits impulses from the cerebral cortex to the intermediate and lateral zones of the cerebellum.

35. Inferior Cerebellar Peduncle

36. Posterior spinocerebellar tract, originates from posterior nucleus. Carries proprioceptive and exteroceptive information from trunk and I/L lower limbs. The cuneocerebellar tract, originating in the external arcuate nucleus transmits proprioceptive information from the upper extremity and neck. The olivocerebellar tract carries somatosensory information from the contralateral inferior olivary nuclei.

37. The vestibulocerebellar tract transmits information from vestibular receptors on both sides of the body. The reticulocerebellar tract arises in the lateral reticular and paramedian nuclei of the medulla. The arcuatocerebellar tract arises from the arcuate nuclei of the medulla oblongata. The trigeminocerebellar tract arises from the spinal and main sensory nuclei of the trigeminal nerve.

38. Fibres entering and leaving through cerebellar peduncles Superior cerebellar peduncle Fibres entering the cerebellum Ventral spino-cerebellar tract Tecto-cerebellar fibres Rubro-cerebellar fibres Trigemino-cerebellar fibres Hypothalamo-cerebellar fibres Fibres leaving the cerebellum Cerebello-rubral fibres Cerebello-thalamic fibres Cerebello-reticular fibres Cerebello-olivary fibres Cerebello-nuclear fibres Some fibres to hypothalamus and thalamus Superior cerebellar peduncle

39. Middle cerebellar peduncle Pontocerebellar fibres Inferior cerebellar peduncle Fibres entering cerebellum Posterior spino cerebellar tract Cuneo-cerebellar tract Olivo-cerebellar fibres Reticulo-cerebellar fibres Vestibulo-cerebellar fibres Anterior external arcuate fibres 7. Trigemino-cerebellar fibres Fibres Leaving the cerebellum Cerebello-olivary fibres Cerebello-vestibular fibres Cerebello spinal and cerebello reticular fibres Middle cerebellar peduncle Inferior cerebellar peduncle

40. Functional organization of cerebellar hemispheres Cerebrocerebellum: Motor planning and coordination Spinocerebellum: Control of ongoing body and limb movements Vestibulocerebellum: Posture, balance, eye movements

41. Somatotopic maps of the body surface in the cerebellum Sensory inputs remain topographically mapped Nearby cerebellar areas control adjacent body parts

42. Functional organization of cerebellar outputs

43. Functional organization of the major ascending outputs from the cerebellum Outputs of deep cerebellar nuclei : Exit the cerebellum through the superior cerebellar peduncle Project direct to subcortical targets Through the thalamus to motor cortex

44. Summary of efferent projections from the cerebellum Ascending: Back to motor and premotor cortex Descending: Superior colliculus : eye movements Reticular formation: planning/correcting movement Vestibular nuclei: balance

45. Stroke Syndromes PICA (40%) Proximal (usually in vertebral arteries) Wallenberg syndrome Distal: Medial branch occlusion will cause acute vertigo and truncal ataxia Lateral branch occlusion :unsteadiness, limb ataxia, and dysmetria without dysarthria

46. Stroke Syndromes AICA (5%) Prominent vertigo, nausea, vomiting, and nystagmus (vestibular nuclei) Ipsilateral facial hypalgesia and thermoanesthesia, and corneal hypesthesia (trigeminal spinal nucleus and tract) Ipsilateral Horner syndrome Contralateral trunk and extremity hypalgesia and thermoanesthesia (lateral spinothalamic tract). Ipsilateral ataxia and asynergia (middle cerebellar peduncle and cerebellum). Ipsilateral deafness and facial paralysis (lateral pontomedullary tegmentum).

47. Stroke Syndromes SCA (35%) Vertigo and vomiting (vestibular nuclei and connections) Nystagmus (MLF and cerebellar pathways) Ipsilateral Horner syndrome Ipsilateral ataxia and asynergia (superior cerebellar peduncle and cerebellum) Ipsilateral intention tremor (dentate nucleus and superior cerebellar peduncle) Contralateral trunk and extremity hypalgesia and thermoanesthesia (lateral spinothalamic) Contralateral hearing impairment (crossed fibers of the lateral lemniscus) Contralateral fourth nerve palsy (pontine tectum)

48. Stroke Syndromes Watershed (20%) Etiologies : focal hypoperfusion secondary to occlusive disease in vertibobasilar vessels, emboli, intercranial atheroma, global hypoperfusion Physical findings variable

49. Stroke Syndromes PICA vs SCA SCA has less frequent vertigo and H/A, both with gait disturbance SCA typically more benign clinically Always need to be aware of possible herniation (tonsillar or transtentorial ) with cerebellar stroke

50. CLINICAL MANIFESTATIONS

51. ATAXIA Ataxia is the cardinal sign of cerebellar disease; Varying degrees of dyssynergia , dysmetria , lack of agonist-antagonist coordination, and tremor. Ataxia may affect the limbs, the trunk, or the gait.

52. Dyssynergia Cerebellar disease impairs the normal control mechanisms that organize and regulate the contractions of the different participating muscles and muscle groups to insure smooth, properly coordinated movement. Lack of speed and skill Lack of integration of the components decomposition of movement the act is broken down into its component parts and carried out in a jerky, erratic, awkward , disorganized manner. multijoint movements co-ordination is impaired

53. Dysmetria Dysmetria refers to errors in judging distance and gauging the distance, speed, power, and direction of movement. Cerebellar dysfunction leads to loss of the normal collaboration between agonist and antagonist. This results in hypermetria ie , over shooting(more common) or hypometria ie , fail to reach the target.

54. Electromyographic studies have shown that dysmetria is associated with abnormalities of the timing and force of antagonist contraction necessary to decelerate the movement.

55. Agonist-Antagonist Coordination A disturbance in reciprocal innervation results in a loss of the ability to stop the contraction of the agonists and rapidly contract the antagonists to control and regulate movement. In patients with cerebellar deficits attempting to make rapid, voluntary movements, the first agonist burst is frequently prolonged, the acceleration time is longer than normal, and the acceleration time may exceed the deceleration time.

56. Impairment of the ability to carry out successive movements and to stop one act and follow it immediately by its diametric opposite causes dysdiadochokinesia , loss of checking movements, and the rebound phenomenon . Inability to rapidly reverse an action also causes impairment of the check response, producing the Holmes rebound phenomenon

57. Tremor The most common type of cerebellar tremor is an intention (active, kinetic, or terminal) tremor that is not present at rest but becomes evident on purposeful movement. Involves the proximal muscles. In severe cases, cerebellar tremor may involve not only the extremities but also the head or even the entire body.

58. Hypotonia Decrease in the tonic output of the cerebellar nuclei, causing loss of cerebellar facilitation to the motor cortex. The muscles are flabby and assume unnatural attitudes; the parts of the body can be moved passively into positions of extreme flexion or extension. Stretch reflexes are normal or diminished Occasionally, the tendon reflexes are “ pendular .” Pendular reflexes are caused by muscle hypotonicity and the lack of normal checking of the reflex response.

59. Dysarthria Articulation may be slow, ataxic, slurred, drawling, jerky, or explosive in type because of dyssynergy of the muscles of phonation. A scanning type of dysarthria is particularly characteristic of cerebellar disease .

60. Nystagmus Indicates involvement of vestibulocerebellar pathways. . Cerebellar disease may cause gaze paretic nystagmus . The patient is unable to sustain eccentric gaze and requires repeated saccades to gaze laterally. With a lesion of one hemisphere, the eyes at rest may be deviated 10 to 30 degrees toward the unaffected side.

61. Other ocular motility disorders include Square-wave jerks, macro square-wave jerks Occular dysmetria opsoclonus

62. CLINICAL FINDING SENSORY ATAXIA CEREBELLAR ATAXIA Loss of vibration and position sense + Areflexia + Nystagmus + Hypotonia + + Ataxia much worse with eyes closed + Past pointing +

63. APPROACH TO ATAXIA Ataxia can arise from disorders of: • Cerebellum (most common) • Sensory pathways (Sensory Ataxia) • Posterior columns, dorsal root ganglia, peripheral nerves • Frontal lobe lesions via fronto-cerebellar associative fibers • Extra pyramidal system • Vestibular system

64. Sensory ataxia 1. loss of distal joint, position sense, 2. absence of associated cerebellar signs such as dysarthria or nystagmus , 3. loss of tendon reflexes, and 4. the corrective effects of vision on sensory ataxia. 5. Romberg sign

65. Frontal lobe ataxia Frontal lobe ataxia refers to disturbed coordination due to dysfunction of the contralateral frontal lobe May resemble the deficits due to abnormalities of the ipsilateral cerebellar hemisphere

66. Vestibular ataxia ataxia associated with vestibular nerve or labyrinthine disease results in a disorder of gait associated with a significant degree of dizziness, light-headedness, or the perception of movement

67. Cerebellar ataxia

68. CEREBELLAR DISEASES IN CHILDHOOD

69. 1.Congenital lesions

70. CHIARI MALFORMATION Displacement of the tonsils and posterior cerebellar vermis through the foramen magnum Compression of spinomedullary junction

71. DANDY WALKER SYNDROME Ballooning of posterior half of 4 th ventricle Lack of patency of foramen of magendie Posterior cerebellar vermis is aplastic Hydrocephalus due to obstruction can develop

72. 2. Metabolic disorders Metachromatic leucodystrophy 2) Refsums syndrome 3) Maple syrup urine disease 4) Hartnup ‘s disease

73. 3. Infectious disorders Acute viral encephalitis Infectious mononucleosis Chicken pox cerebellitis

74. 4. Degenerative disorders Friedreich’s ataxia Other inherited cerebellar ataxia- 1.Olivpontocerebellar ataxia 2. Dentatorubrothalamic degeneration 5. Tumors Medulloblastoma Astrocytoma

75. CEREBELLAR DISEASES IN THE ADULT

76. ACQUIRED ATAXIA HYPOTHYROIDISM TOXIC CAUSES INFECTIOUS AND TRANSMISSIBLE DISEASES AUTOIMMUNE CAUSES

77. TOXIC CAUSES 1.ALCOHOL direct toxic action of alcohol and associated vitamin deficiency –B1. Progressive truncal ataxia with gait disturbances of cerebellar type Imaging- anterior superior vermian atrophy

78. 2.CHEMOTHERAPEUTIC AGENTS- 5FU and Cytosine arabinoside 3.HEAVY METALS- Organic mercury poisoning and lead poisoning, bismuth and lithium toxicity 4.SOLVENTS- spray paint and paint thinners such as toluene 5. ANTICONVULSANT- most commonly phenytoin

79. INFECTIOUS AND TRANSMISSIBLE DISEASES 1.Brainstem encephalitis/ BICKERSTAFF syndrome ataxia ophthalmopegia lower CN palsy 2.HIV infection- lymphoma, PML, chronic meningeal infection , toxoplasmosis 3. Creutzfeld Jakob disease 4.CNS Whipple disease

80. AUTOIMMUNE CAUSES 1.Paraneoplastic cerebellar degeneration - rapidly progressive pancerebellar syndrome MRI-atrophy of entire cerebellum CSF- mononuclear pleocytosis 2. Ataxia and anti glutamic acid decarboxylase antibodies 3. Ataxia and gluten sensitivity 4.Superficial siderosis

81. INHERITED CEREBELLAR DISEASES Most of the cerebellar ataxias begin in middle age 3 major groups 1. Friedreich’s ataxia 2. Dominant inherited ataxia 3. Recessively inherited ataxia

82. FRIEDREICH’S ATAXIA Familial Inherited as recessive with incidence of 1:100,000 Classic form and genetically determined vit E deficiency syndrome Age of onset is constant and ranges from 8 to 16 years 9q13 Mutant gene frataxin Expanded GAA repeats in >95% of patients

83. CLINICAL FEATURES In childhood a high arched foot with hammer toes may be found- Friedreich’s foot Scoliosis Cerebellar component- dysarthria and ataxia, nystagmus uncommon ECG- inverted T waves and ventricular hypetrophy Degeneration of peripheral nerves- Areflexia

84. Damage to corticospinal pathway- extensor plantar Cardiac pathology (90%) consists of myocytic hypertrophy and fibrosis, focal vascular fibromuscular dysplasia A high incidence 20% of Diabetes mellitus is seen in association with insulin resistance and pancreatic beta cell dysfunction.

85. Management Vitamin E therapy for Vit E deficient form of disease IDEBENONE a free radical scavenger can improve cardiac hypertrophy

86. image

87. Pes cavus

88. DOMINANT INHERITED ATAXIA Many variants of dominant inherited ataxia of LATE onset with varied clinical picture are identified Now named as Spinocerebellar ataxia . SCA 1 to 40

89. SCA CAG triplet repeat expansions in various genes SCA 1 to 40 CAG encodes Glutamine Polyglutamine proteins ataxins toxic to neurons neuronal loss and gliosis

90. SCA 1 OPCA Onset- early to middle adult life s/s- cerebellar , extrapyramidal and dementia in late stages Pathology- marked shrinkage in the ventral half of pons , olivary eminence of medulla and cerebellar atrophy

91. SCA3- MACHADO JOSEPH DISEASE Types I, II and III Mean age of onset is 25 years Neurologic deficits invariably progress to death within 15 years of onset SPARING OF INFERIOR OLIVES DISTINGUISHES MJD from other dominant ataxia

92. SCA7 Disorder is distinguished from other SCA by retinal pigmentary degeneration

93. Common features of SCA Ataxia of gait is universal At first there is pyramidal signs, increased reflexes and spasticity Later reflexes disappear to be replaced by cerebellar hypotonia Dysphagia and dysarthria early Sphincter disturbances occur early Extrapyramidal symptoms and dementia occur late in the course leading to disability Time course is variable Some cases progress to death within 1 to 2 years of onset MRI- diagnostic demonstrating atrophy of pons and cerebellum

94. RECESSIVE INHERITED ATAXIA Metabolic and childhood ataxia Wilson’s disease Refsum’s syndrome

95. METABOLIC CEREBELLAR DISEASE PURKINJE CELL LOSS ALCOHOL is the commonest cause leading to reversible ataxia during acute intoxication severe acute irreversible ataxia in Wernicke’s encephlopathy CO poisoning and acute hyperthermia may produce acute destruction of cerebellar cortex Anticonvulsant drugs case acute reversible ataxia

96. NEOPLASM Metastatic malignant disease From lungs, breast, large bowel Directly to cerebellum via paravertebral venous plexus up the spine and into the posterior fossa Primary tumor Rare Benign hemangioblastoma Excellent prognosis

97. MULTIPLE SCLEROSIS Cerebellar signs in MS are common Lesions in brainstem cerebellar pathways INO, long tract signs and pyramidal signs are seen

98. REFERENCES Harrison’s Principles of internal medicine, 20 th edition Bradley’s neurology in clinical practice, 7 th edition John Patten, Neurological differential diagnosis, 2 nd edition DeJong’s neurological examination, 7 th edition

99. THANK YOU