Tizanidine for the treatment of intention myoclonus: a case series

OBJECTIVE: To evaluate the effectiveness of tizanidine in treating intention myoclonus. DESIGN: Case series. SETTING: Inpatient rehabilitation center. PARTICIPANTS: Three subjects whose activities of daily living were impaired due to intention myoclonus related to mitochondrial encephalomyopathy, stroke, and multiple sclerosis (MS). INTERVENTION: Tizanidine. MAIN OUTCOME MEASURES: Reduction in intention myoclonus and change in score on the FIM instrument. RESULTS: The patient with mitochondrial encephalomyopathy had left upper- and lower-extremity intention myoclonus; the patient with stroke had left upper intention myoclonus; and the patient with MS had right upper- and left lower-intention myoclonus. In the patient with mitochondrial encephalomyopathy, the FIM score increased from 90 to 103 points over 2 days of tizanidine. The stroke patient's FIM score improved only from 74 to 79 after 4 weeks of tizanidine. The patient with MS improved from 83 to 101 after 6 days of tizanidine. All 3 patients had almost full resolution of the intention myoclonus. All continued on tizanidine except the patient with stroke, who had minimal gains and a low systolic blood pressure. None of the patients experienced significant sedation or hypotension. CONCLUSIONS: Tizanidine may be a safe and effective option for treating intention myoclonus that occurs in a variety of neurologic conditions.     

Hereditary essential myoclonus in a large Norwegian family

We examined 56 members of a large Norwegian family with hereditary essential myoclonus, affecting mainly the neck and upper parts of the body, and inherited in an autosomal-dominant pattern. We observed definite myoclonus in nine individuals, probable myoclonus in one, and possible myoclonus in one. There were two other living members who had a history compatible with myoclonus but who had developed a permanent remission, so we did not observe the movements, and two who had involuntary movements only with stress. Writing usually increased the myoclonus in the neck and trunk, but did not produce myoclonus in the arm used for writing. Having a conversation with an individual who was aware of being watched would also usually increase the myoclonus. Alcohol ameliorated the myoclonus in many, but not all, affected members. Activities such as walking and concentrating during reading would usually reduce the myoclonus. Three living members with definite myoclonus also had features of mild focal dystonia, either spasmodic torticollis or blepharospasm, indicating that focal dystonia may exist as part of the clinical spectrum in hereditary essential myoclonus. In addition to examining the members of the family, we videotaped them and obtained blood samples for molecular genetic analysis.     

Life-threatening status epilepticus following gabapentin administration in a patient with benign adult familial myoclonic epilepsy

We report the case of a 57-year-old man who experienced life-threatening myoclonic status after the administration of gabapentin. Based on familial data, the patient was determined to be a member of a previously described family with benign adult familial myoclonic epilepsy (BAFME). The myoclonic status did not respond to benzodiazepines, but resolved after discontinuing the gabapentin. As for other idiopathic generalized epilepsies, gabapentin may precipitate myoclonic status in a benign syndrome, such as BAFME, as is reported herein for the first time. A correct diagnosis and prompt discontinuation of the drug may reverse a potentially severe, life-threatening condition.     

Benign adult familial myoclonic epilepsy (BAFME): evidence of an extended founder haplotype on chromosome 2p11.1-q12.2 in five Italian families

Benign adult familial myoclonic epilepsy (BAFME or FAME) is an autosomal dominant condition, characterized by shivering-like tremors of cortical origin, myoclonus, and epilepsy. Linkage to chromosomes 2p11.1-q12.2 and 8q23.1-q24.11 has been reported in Japanese and Italian families, respectively. We aimed to determine whether a common founder haplotype was shared by five BAFME families from southern Italy and attempted preliminary genotype-phenotype correlation analyses. Five Italian BAFME families were identified. One family has not been previously reported. DNA from 53 affected individuals was genotyped with highly polymorphic microsatellite markers spanning chromosomes 2p11.1-q12.2 and 8q23.1-q24.11. Multipoint linkage analysis was performed using LINKMAP 5.1 software assuming an autosomal dominant trait with 0.99 penetrance and frequency of 0.001. Significant linkage was found on chromosome 2p11.1-q12.2 and a maximum cumulative lod score of 18.5 was found for markers D2S2161 and D2S388. The haplotype "5332" of adjacent markers D2S388, D2S2216, D2S113, and D2S2175 segregates with the disease in all families indicating that the same mutation inherited from a common ancestor segregates in these families. Preliminary genotype-phenotype showed that patients carrying the disease haplotype show minor clinical differences, suggesting that expressivity of the founder mutation is not markedly influenced by other factors. The identification of causative mutations in BAFME requires an extensive and collaborative screening effort.     

Myoclonic Alcoholic Epilepsy

We describe 2 patients with chronic alcoholism who over a period of several years developed epilepsy associated with a cerebellar syndrome and action myoclonus. The clinical picture suggested progressive myoclonic epilepsy, but subsequent investigations did not confirm this diagnosis. Myoclonus worsened during abstinence and was relieved during indulgence. We believe that this special clinical syndrome should be recognized as a complication of chronic alcoholism.     

Opsoclonus-myoclonus-ataxia syndrome with autoantibodies to glutamic acid decarboxylase

Opsoclonus-myoclonus-ataxia syndrome (OMS) is a rare neurological disorder of probably autoimmune origin. Most cases are associated with a remote neoplasm or a viral infection; however in some instances no underlying aetiology can be demonstrated. We report the presence of anti-glutamic acid decarboxylase antibodies (anti-GAD Abs) in the serum and CSF of a patient with idiopathic OMS. Treatment with intravenous immunoglobulin led to a remarkable clinical improvement with parallel reduction of anti-GAD titers. Anti-GAD Abs have been associated with several neurological syndromes. They could also be responsible for the clinical triad of OMS, by impairing GABAergic transmission in specific brainstem and cerebellar circuits. We propose that testing for anti-GAD Abs should be performed in OMS, especially when no other aetiological association can be demonstrated.     

Adult Postanoxic "Erratic" Status Epilepticus

A 66-year-old woman with posttraumatic anoxic coma after diffuse cerebral fat embolism had continuous alternating-side myoclonic jerks. Usually, this kind of myoclonic status epilepticus (SE) occurs in newborn infants. We postulate the unusual combination of diffuse cerebral anoxia plus commissural fiber damage as a possible explanation.     

Cortical myoclonus in huntington's disease associated with an enlarged somatosensory evoked potential

We report the electrophysiologic findings of myoclonus in a patient with Huntington's disease (HD). This patient was studied postoperatively after a bilateral fetal cell transplant in his striatum. Incomplete transient improvement was seen in the myoclonus, followed by gradual deterioration. The myoclonus itself had a cortical correlate and was associated with an enlarged somatosensory evoked potential (SEP), consistent with the presence of cortical reflex myoclonus. An enlarged SEP has not been previously reported in myoclonus associated with HD. The postulated mechanisms for myoclonus, when it occurs in HD, have differed in the literature. The reason for the transient improvement of the myoclonus following transplantation is unclear, but this case raises the possibility that basal ganglia circuits may modulate cortical myoclonic activity.     

Coexistence of Unverricht-Lundborg disease and congenital deafness: Molecular resolution of a complex comorbidity

Purpose :  We report on genetic analysis of a complex condition in a Serbian family of four siblings, wherein two had progressive myoclonic epilepsy (PME) and congenital deafness (CD), one had isolated congenital deafness (ICD), and one was healthy.
Methods and Results :  Molecular diagnosis performed by Southern blotting confirmed Unverricht-Lundborg disease in the available sibling with PME/CD. In the sibling with ICD (heterozygote for expansion mutation in CSTB ) we demonstrated recombination event between the D21S2040 marker and the CSTB gene and identified c.207delC (p.T70Xfs) mutation in the fourth exon of the transmembrane protease, serine-3 (TMPRSS3) gene (maps in close proximity to CSTB), responsible for nonsyndromic deafness in the sibling with PME/CD as well.
Discussion :  To the best of our knowledge this is the first genetic confirmation of the coexistence of these two mutations.     

Postanoxic Myoclonus: Two Case Presentations and Review of Medical Management

Postanoxic myoclonus is a rare manifestation after an anoxic event, with fewer than 150 cases reported in the literature. The condition is characterized by myoclonic jerks, which are worse on action than at rest, and postural lapses, ataxia, and dysarthria. The disability caused by postanoxic myoclonus can be profound, and treatment in the rehabilitation setting is exceptionally challenging. We present 2 patients who suffered from postanoxic myoclonus after an anoxic event, both of whom were successfully treated with a combination of levetiracetam, valproic acid, and clonazepam. These cases act as a framework for discussing the management of postanoxic myoclonus in the clinical setting.