movement disorders in multiple sclerosis.pptx

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1. Movement disorders in multiple sclerosis and other demyelinating disorders By Mohamed Hamed Assistant lecturer in neurology department

2. Introduction Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating disease of the central nervous system characterized pathologically by multifocal areas of demyelination and subsequent scarring. The clinical diagnosis of MS requires dissemination of the lesions in time and space. Tremor is the most frequent movement disorder in MS other movement disorders have been described in about 1.6% of MS patients

3. 1- T remors Tremor has been reported to occur in 25.5% to 58% of MS patients and is considered disabling in 3% to 15 %. Tremor in MS involves most frequently the arms, but it can also involve the legs, head, neck, vocal cords or trunk . Involvement of the tongue, jaw or palate has not been reported. The two most prevalent tremor forms in MS are postural and intention tremor

4. The exact strategic location of a tremor-inducing demyelinating plaque is unclear but seems to involve the cerebellum, the lateroventral or centromedian thalamic nuclei, or their connections. Since involvement of the cerebellum, brainstem or both is seen in up to 81.6% cases of MS at some time during the illness, it is not surprising that tremor is so commonly seen in these patients.

5. Medical ttt : Primidone , propranolol, carbamazepine, gluthetimide , intrathecal baclofen and high dose isoniazid have been reported to show some beneficial effect on tremor in MS patients. Stereotactic surgery , either ablative or as deep brain stimulation (DBS ) has also been studied. Overall, thalamotomy improves the tremor immediately in almost all patients, with sustained benefit at 1 year in 70% [3], while thalamic DBS reduced tremor at one year in 69 % to 100% of patients

6. 2-Paroxysmal dystonia Also called painful tonic spasms , represent the second most frequent movement disorder described in MS after tremor . These attacks are stereotyped , usually last from 30 s to 5 min and can occur up to 100 times a day for a period of several weeks. They typically consist of asymmetric extension posturing of the legs and arms with opisthotonus and facial contractions. They are often painful and can be preceded by a sensory aura in either the affected or the contralateral limbs. They can be provoked by hyperventilation, startling noise , tactile stimulation or voluntary movement

7. It is described with lesions of the cervical spinal cord, brainstem, cerebellum, cerebellar peduncles, cerebral peduncles, thalamus, subthalamic nucleus, internal capsule, and basal ganglia. Although some have postulated an epileptic origin , despite normal electroencephalogram. These tonic spasms a result of transversely spreading ephaptic activation of axons. Paroxysmal dystonia can be treated or prevented by carbamazepine, acetazolamide and other anticonvulsant drugs, although no controlled trials have been published .

8. The types of dystonia described in association with MS include cervical dystonia, dystonic writer's cramp, sustained hand dystonia, blepharospasm, oromandibular dystonia, generalized dystonia and hemidystonia. Poor anatomical correlation between the MS-related deficit and the site of dystonia. Some reports describe cerebellum and brainstem atrophy or cervical demyelinating lesions anatomically and temporally related to the dystonia. If dystonia persists despite the use of immunosuppressant medication , a symptomatic treatment with anticholinergics, baclofen , muscle relaxants or botulinium toxin injections. 3-Dystonia

9. 4-Ballism and chorea Chorea consists of irregular, purposeless, abrupt, rapid, jerky, un sustained movements that flow randomly from one part of the body to another. Ballism is a brief, involuntary, flinging or throwing movement of an extremity. Ballism and chorea rarely reported in MS patients, and almost never as the presenting symptom . Disappeared in almost half of the reported cases, consistent with an attack of MS .

10. Patients with hemiballism had a plaque of demyelination in the subthalamic nucleus and patients with chorea had lesions in the basal ganglia, especially the striatum. If does not resolve with the resolution of the MS attack and persists despite the use of immunosuppressant medication, a symptomatic treatment with dopamine receptor blockers or tetrabenazine might be needed

11. 5-Paroxysmal kinesigenic dyskinesia (PKD) characterized by episodes of uni- or bilateral choreo-athetosis occasionally preceded by a sensory aura. precipitated by sudden or rapid movements, startle or hyperventilation. Usually considered an episodic movement disorder with autosomal dominant inheritance caused by mutations in the PRRT2 gene. PKD has been reported in a few cases of MS. The lesions reported in MS-related PKD cases included the contralateral thalamus, lentiform nuclei, globus pallidus , internal capsule, mesencephalic peduncle and cervical cord

12. The observation that PKD in some MS patients improves with anticonvulsants such as phenytoin, carbamazepine or acetazolamide suggests a common pathophysiology with the genetic form of PKD, and that PKD could be a form of subcortical epilepsy possibly caused by a demyelinating lesion. some authors object that symptom control is achieved at sub-therapeutic plasma levels of antiepileptic drugs, and that PKD is more an extrapyramidal disorder than a form of epilepsy

13. 6-Parkinsonism Parkinsonism is a disorder characterized by the clinical tetrad of rest tremor, rigidity, akinesia (or bradykinesia) and postural instability (TRAP). To date, at least 23 cases of parkinsonism have been described in patients with MS, but a causal relationship was evident with a high degree of certainty only in 8 cases. The MS-related cases of parkinsonism were similar to those with idiopathic Parkinson's disease, but they had other neurological symptoms that were attributed to MS

14. The relationship between parkinsonism and MS in these cases was supported by: 1- a rapid onset. 2- strategically located demyelinating lesion in the bilateral thalamus and globus pallidus or in the vicinity of the substantia nigra, 3- almost complete resolution of extrapyramidal signs after a course of corticosteroids. There was a good response to dopaminergic drugs when the lesion involved the substantia nigra , but not when the thalamus and globus pallidus were bilaterally affected

15. 7-Myoclonus Myoclonus refers to sudden, involuntary, brief, irregular “ shock like ” contractions (positive myoclonus) or inhibition of contraction (negative myoclonus) of certain muscle groups. In addition to generalized or multi-focal myoclonus, this movement may be localized to one body area, such as the palate, limb or trunk, hence the term “segmental myoclonus”. Palatal myoclonus is a rhythmic palatal movement at about 1.5–3 Hz. It is secondary to a lesion in the dentato – rubro – olivary pathway also known as Mollaret's triangle. Palatal myoclonus has been documented in MS but a lesion of the dentate– rubro – olivary pathway was not found in these patients although a brain MRI did show a plaque in the pons of one patient

16. 8-Hemifacial spasm and continuous facial myokymia Hemi-facial spasm (HFS) is characterized by synchronous spasms of one side of the face. Only a few case of HFS in MS patients have been described in the literature. Some were associated with lesions in the region of the ipsilateral facial nucleus, while others did not have brainstem lesions but responded to intravenous methylprednisolone. Sustained unilateral contraction of the facial muscles associated with mild ipsilateral facial paresis has been rarely reported in patients with MS and attributed to lesions in the vicinity of the facial nucleus

17. Continuous facial myokymia (CFM) is a rare involuntary undulating and vermicular movement spreading across facial muscles . When present in MS patients, It is most often unilateral but can be bilateral. Is associated with a brainstem lesion specifically affecting the post-genu portion of the ipsilateral facial nerve in 90% of the cases. Radiological brainstem lesions typically improve with clinical resolution of CFM

18. The presence of unexplained peripheral facial palsy associated with HFS in some patients might be secondary to intra-dural facial nerve demyelination. If the HFS or CFM persists despite resolution of the attack and the use of immunotherapy , symptomatic treatment with botulinum toxin injection can be useful,

19. Tourettism can be defined as a combination of motor and phonic tics that would otherwise meet the criteria for Tourette's syndrome but are secondary to another neurological or general disorder. Only 3 cases of tourettism in MS have been published: one patient with a simple phonic tic characterized by throat-clearing sounds (MRI showed demyelinating lesions involving the thalamus and basal ganglia and who responded to pimozide). Another patient with MS suggested by imaging exhibited complex phonic tics that improved with dronabinol. One patient with phonic and motor tics as well as impulse control and self-injurious behavior 5 years after onset of MS improved on quietapine. Demyelinating lesions in the brainstem, middle cerebellar peduncles and both thalami. 9-Tourettism

20. 10-Restless legs syndrome Restless legs syndrome (RLS) is characterized by discomfort in the legs that is worse at night and during inactivity and improves with movement or walking. A 2 to 5.5 fold increase in the prevalence of RLS in MS patient has been reported in some studies, and a systematic review and meta-analysis showed a 4-fold increase in frequency of RLS among patients with MS compared to controls. RLS also seems more severe in MS patients.

21. RLS seems secondary to the inflammatory component of MS rather than the axonal degeneration, with no clear anatomical correlation but decreased fractional anisotropy in otherwise normal appearing cervical cord. However , well known cause of RLS (pregnancy, iron deficiency anemia , uremia and diabetes) should be excluded in a MS patient before attributing RLS to MS.

22. Key et al. described a patient with a complex hyperkinetic movement disorder characterized by tremor, dystonia, ballism and HFS . It started 8 years after onset of relapsing–remitting MS that had evolved into secondary progressive MS and did not respond to interferon beta-1a , mitoxantrone, levodopa (375 mg/day) clonazepam (6 mg/day) or biperiden (12 mg/day). Her brain MRI showed extensive periventricular and subcortical hemispheric demyelination as well as lesions in the basal ganglia, thalamus and brainstem. hyperkinetic movement. disorders have been reported in very few other MS patients and were a combination of tremor and ballism 11-Complex hyperkinetic movement disorder