The cognitive features of idiopathic and DYT1 dystonia.

Dystonia is a common movement disorder. In this paper, we review the literature on cognitive function in idiopathic and DYT1 dystonia. In idiopathic or DYT1 dystonia, cognition is largely intact with only isolated executive dysfunction. Dystonia patients also have increased temporal and spatial discrimination thresholds, considered endophenotypes of the disorder because deficits are also shown by unaffected relatives and nonmanifesting carriers of the DYT1 mutation. Anticholinergic medication in high doses can be associated with memory impairment in dystonia. The successful treatment of dystonia with botulinum toxin injections or deep brain stimulation does not produce any major adverse effects on cognition. The aspects of cognition that require further investigation in future studies of dystonia include inhibitory control, decision making, and social cognition. © 2017 International Parkinson and Movement Disorder Society.

Atypical presentations of DYT1 dystonia with acute craniocervical onset.

DYT1 gene mutations lead to early-onset dystonia that begins with focal limb onset and spreads to other body regions within 5 years, with typical sparing of the oromandibular muscles. In the present study, we describe two patients with an unusual presentation of the disease.

Widespread nevus spilus associated with torsion dystonia: a case report.

Usually speckled lentiginous nevus or nevus spilus is a small solitary lesion consisting of a light tan patch with numerous dark brown macules or papules (or both) within it. It is occasionally associated with complex birth defects such as phacomatosis pigmentovascularis, phacomatosis pigmentokeratotica, or speckled lentiginous nevus syndrome. Uncommon presentations include large segmental lesions that may or may not be systematized and can sometimes be associated with other anomalies. We hereby report a 6-year-old Caucasian patient with systematized nevus spilus associated with torsion dystonia, a combination not published thus far.

Congenital mesenteric abnormality causing death in an infant with a concurrent diaphragmatic hernia.

The principle causes of infant death are natural causes [including the Sudden Infant Death Syndrome (SIDS)]. Natural deaths in infants are principally due to infections, cardiovascular anomalies and other metabolic or genetic disorders. Gastrointestinal pathology including anomalies may also cause death in this age group. This case describes a 6 month old boy who had undergone repair of a diaphragmatic hernia when aged 2 days, but who subsequently died as a result of a mesenteric abnormality with torsion of the gut and a large fibrous walled bowel containing hernial sac in the left pleural cavity.

Defective temporal processing of sensory stimuli in DYT1 mutation carriers: a new endophenotype of dystonia?

DYT1 primary torsion dystonia is an autosomal dominant movement disorder due to a 3-bp GAG deletion in the TOR1A gene, which becomes manifest in only 30-40% of mutation carriers. Investigating the factors regulating this reduced penetrance might add new insight into the mechanisms underlying the disease. The pathophysiology of dystonia has been related to basal ganglia dysfunctions that lead to the most prominent motor symptoms. However, subclinical sensory deficits have also been reported, particularly in adult-onset focal dystonia. Sensory abnormalities in different forms of sporadic dystonia have been revealed by using a psychophysical method, namely, the temporal discrimination threshold (TDT), quantified as the shortest time interval at which the two stimuli are perceived as separate. Little or no information about the presence of sensory abnormalities in DYT1 gene manifesting and non-manifesting carriers is available. With the aim of disclosing possible associations between sensory deficits and the DYT1 mutation, we assessed TDTs of DYT1 manifesting patients (n = 9); DYT1 non-manifesting relatives (n = 11); non-carrier relatives (n = 9); external control subjects (n = 11). Pairs of tactile, visual or visuo-tactile stimuli were delivered in blocked, counterbalanced order. Intervals between stimuli increased from 0 to 400 ms (in 10 ms steps). On each trial, subjects had to report whether stimuli occurred simultaneously or asynchronously. We measured the first out of three consecutive inter-stimulus intervals at which subjects recognized the two stimuli as temporally separated (TDT) and the first of three consecutive intervals at which they also reported correctly which stimulus in the pair preceded (or followed) the other temporal order judgment (TOJ). Results showed higher tactile and visuo-tactile TDTs and TOJs in DYT1 carriers, both manifesting and non-manifesting, compared with non-carrier relatives and with external control subjects (for all comparisons, P < 0.039). This finding indicates that the DYT1 mutation determines subclinical sensory alterations, which could be disclosed by a psychophysical task. Moreover, these results have the notable implication that sensory deficits in dystonia are not a mere consequence of abnormal movements, but they may even occur before overt clinical manifestations, representing a subclinical phenotype in DYT1 mutation carriers.

Severe dystonia and myoglobinuria.

Myoglobinuria may follow extreme muscular exertion or disorders that cause muscle necrosis. Dystonia has not been implicated previously. We studied an 8-year-old boy of non-Jewish, Mexican-American descent with autosomal-dominant dystonia musculorum deformans who developed rapidly progressive and severe generalized dystonia, hyperpyrexia, myoglobinuria, and renal failure. Curarization was required. Transient improvement was achieved with tetrabenazine and baclofen, but bilateral thalamotomy was then performed. Patients with severe dystonia should be observed for evidence of myoglobinuria.

Treatment of cerebral origin spasticity with continuous intrathecal baclofen delivered via an implantable pump: long-term follow-up review of 18 patients.

OBJECT: The goal of this study was to assess the long-term benefits of managing severe spasticity by using continuous infusion of intrathecal baclofen delivered via an implantable pump. METHODS: Eighteen patients with severe spasticity of cerebral origin, who failed to respond adequately to more conservative treatments, have-been treated with continuous infusion of intrathecal baclofen delivered via an implanted pump. Follow-up review of these patients has lasted between 12 months and 9 years. The patients have been assessed using a variety of tools. Seventeen have had a significant reduction in tone and all have benefited by a reduced need for nursing care or increased function or both. CONCLUSION: Long-term continuous infusion of intrathecal baclofen delivered via an implantable pump offers an effective method for dealing with otherwise intractable spasticity.

The correction of spinal deformity in idiopathic torsional dystonias.

The torsional dystonias constitute a group of motion disorders of unknown etiology with variable onset, progression, and severity that frequently result in spinal curvature. Four patients with this uncommon disorder, with curves averaging 70 degrees (range, 55 to 95 degrees), underwent surgical correction for progressive spinal deformity. All of them had improvement in function postoperatively, but there was a high rate of postoperative complications.

The natural history of dystonia.

We have analyzed 226 patients with a diagnosis of dystonia musculorum deformans seen in our clinica between 1955 and 1974. These were evenly divided between male and female, but of the 226 patients, 225 were white and only one was black. Forty-two percent were Jewish, as contrasted with 3% Jewish population in the United States. It is interesting to note that a family history was obtained in 28% of both the Jewish and the non-Jewish groups. Thirty of the patients reported a significant viral infection within 3 months preceding the onset of symptoms. Only six patientss had a history of one or more remissions during the course of their illness. The mean duration of symptoms before examination in this series was 8.6 years with a duration of 1 to 42 years. Fifty-six of the patients had been diagnosed as having conversion hysteria at some time during the course of their illness. The majority of the patients had the onset of symptoms between the ages of 5 and 10, although the age span was from 2 to 45 years of age. Seventy-six of the patients had an IQ statistically significant above average (3). Each symptom, rate of progress of the disease, and various other factors in the history were corrolated with age, sex, ethnic group, mode of onset, and 20 other variables. The most pertinent subgroupings affecting the natural history were the age on onset and the ethnic group and family history. Trunkal involvement was most common in the non-Jewish group with a positive family history. This particular sub-group of patients showed predominately midline symptomatology. In the groups below the age of 13, the onset was almost invariably in one of the four limbs. However, in the group 14 years of age and older, 30% had their initial dystonic symptoms in the neck and a total of 40% of the patients whose onset was at age 14 or later, had marked nuchal symptoms. This clear-cut predominance of limb involvement in the youngest groups is also indicated by the observation that 38% in the youngest group had become confined to a wheelchair because of gait abnormalities, whereas none of those whose age of onset was 14 or older were disabled to this degree by gait abnormality. The most rapidly progressive and incapacitating symptomatology was seen in those patients with onset of symptoms below the age of 8 so that in general the younger the age at onset, the more rapid the progress of the symptoms.

Idiopathic torsion dystonia and writing tremor within a family.

A 12-year-old boy had suffered from idiopathic torsion dystonia since the age of 8 years, which had never been relieved with pharmacologic treatment. His mother had exhibited primary tremor upon writing from the age of 10 years, but had not yet developed dystonia. Surface electromyography revealed paradoxical muscular contraction of Westphal in both patients, although the main abnormal findings in the proband and his mother were continuous tonic discharges in the arms and 4-5-Hz grouped discharges in the neck, respectively. The simultaneous occurrence of dystonia and writing tremor within one family, and the presence of the paradoxical contraction in both cases suggest that a certain type of dystonia and writing tremor may be pathogenetically linked.

Rhabdomyolysis due to hereditary torsion dystonia.

Following an acute dystonic crisis, a 6-year-old boy with hereditary torsion dystonia developed rhabdomyolysis. To our knowledge, hereditary torsion dystonia has never been reported as a cause of rhabdomyolysis. Early diagnosis and treatment of rhabdomyolysis should be considered in children with severe dystonia in order to prevent renal failure.

Spinal lordosis with marked opisthotonus secondary to dystonia musculorum deformans: case report with surgical management.

STUDY DESIGN: A case report of severe spinal lordosis with marked opisthotonus and retrocollis secondary to dystonia musculorum deformans is presented. OBJECTIVE: To describe a case of dystonia musculorum deformans with progressive spinal lordosis and its surgical treatment. SUMMARY OF BACKGROUND DATA: Four patients with correction of coronal spinal deformity associated with dystonia musculorum deformans have been reported in the literature. No reports of sagittal spinal deformity treated with surgical instrumentation and fusion were found. METHODS: A retrospective chart and radiographic review of a single case was conducted. RESULTS: Orthotic management and pharmacologic therapy with botulinum toxin injections were unsuccessful in controlling the deformity. Severe spinal lordosis (170 degrees ) from occiput to sacrum was corrected surgically, allowing an upright posture. CONCLUSION: Dystonia musculorum deformans is a rare condition resulting in coronal or sagittal plane deformities. When other treatment methods are unsuccessful, surgical instrumentation and arthrodesis may correct the deformity and improve function.

Oral rehabilitation using osseointegrated implants in a patient with idiopathic torsion dystonia.

Idiopathic torsion dystonia is a motor syndrome characterized by dystonic movements and postures in the absence of other neurologic deficits. The condition involves prolonged spasms of muscle contraction that distort the body into typical postures. Such distortions involving the head and the neck make conventional denture use in edentulous patients very difficult. The present paper reports on a patient with idiopathic torsion dystonia who was treated with a mandibular overdenture supported by endosteal implants, which enabled the establishment of a stable occlusion and improved the dynamics of the masticatory muscles for chewing.

[Torticollis as an initial symptom of adult-onset dystonia musculorum deformans].

Dystonia musculorum deformans (DMD) is an idiopathic movement disorder which usually involves pediatric age group and progresses to the generalized type. On the contrary in adult-onset DMD, dystonia is usually confined to an upper extremity and its clinical course is benign. The authors report seven patients with adult-onset DMD whose initial symptom was confined to the neck. Diagnosis of idiopathic spasmodic torticollis had been made in all of them. Average ages at the onsets of torticollis and extranuchal dystonia were 49 +/- 13 and 54 +/- 9 years (mean +/- SD) respectively. The duration between these onsets was 2-3 years in five patients and 10-17 years in two younger patients. Two patients finally developed generalized dystonia and one patient became hemidystonic type. These findings suggest that some patients diagnosed as idiopathic spasmodic torticollis are in an early stage of DMD and that this particular type progresses more likely to the generalized form than other types of adult-onset DMD.

[A case of idiopathic torsion dystonia showing blepharospasm at the onset].

We report a 12-year-old boy with idiopathic torsion dystonia. Blepharospasm appeared at the age of 10, followed by truncal hypertonia and progressive scoliosis after 1 year. He had bizarre involuntary movement of his limbs upon waking, which was initially misinterpreted as a psychogenic reaction. Routine neurological examinations revealed no abnormality. Treatment with diazepam, bacrophen, 1-dopa, and clonazepam, led to only short time improvement of symptoms. At the age of 14, his symptoms gradually improved in natural course. At present he is 15 years old, and capable of normal daily activities. His clinical course was not typical of idiopathic torsion dystonia and very rare in children.

[Dopamine deficiency syndrome in children with specific reaction to the treatment with levodopa preparations]. / Sindrom dofaminovoi nedostatochnosti u detei s osoboi reaktsiei na lechenie preparatami levodopy.

The authors describe the dopamine deficiency syndrome in children with the disease beginning during their first year and peculiar dystonia++ symptoms resulting in a total immobilization and speech loss. All the symptoms of the disease can be removed by low doses of Nakom and reappeared upon the drug withdrawal. Tyrosine hydroxylase studies performed in these patients at various stages of the disease showed an unusual pattern of the enzyme activity differing from that seen in children with similar pathology failing to improve dramatically under the Nakom treatment.

[The surgical results in patients with different forms of torsion dystonia]. / Rezul'taty khirurgicheskogo lecheniia bol'nykh s razlichnymi formami torsionnoi distonii.

The paper describes stereotactic operations made in 278 patients with different forms of torsion dystonia during 20 years. Late outcomes were studied and assessed in 130 patients. The duration of follow-ups was 3 to 23 years. The patients' mean age at surgery was 30.5 years. The indications for surgical treatment were ineffective medical treatment and progressive disease. Positive early and late postoperative outcomes were achieved in 93 and 70% of patients, respectively. Complications developed in 3.2 and 12.3% of patients after the first and second operations, respectively. The positive outcome depends on the form, etiology, the destructible structure or a complex of structures. Surgical treatment of patients with torsion dystonia by stereotactic operations on basal ganglia is an effective treatment that provides a steady-state positive result in 70% of patients in the late period.

[Cognitive functions in patients with primary torsion dystonia treated with pallidal deep brain stimulation].

Forty-three patients with primary dystonia underwent neuropsychological assessment according to the method of A.R. Luria. Twenty-three patients with generalized dystonia and 20 with local forms (cervical and craniocervical) were included in the study. All patients were evaluated before pallidal deep brain stimulation (DBS GPi), 32 patients were examined 3-6 days after surgery, and 26 patients - during the first two years of the postoperative follow-up. The evaluation before surgery revealed cognitive impairment in 41 patients. The most common were mnemonic impairment, inertness and preservation in different tests, and spatial function decline. Thus, patients with local forms more frequently had troubles with performance memory tests, whereas spatial function disorders were more common in patients with generalized forms. The deterioration of cognitive functions was observed in 28 patients in the early postoperative period. Moreover, the group of patients with local forms had poorer results. The neuropsychological evaluation after 3-6 months of the postoperative follow-up showed the restoration of cognitive functions to the preoperative level. Neuropsychological syndrome observed in patients with dystonia was generally similar to that found in patients with lesions of the frontal lobe, the caudate nucleus, and the cerebellum.

Fat embolism syndrome in a child with dystonia musculorum deformans.

A 16-year-old boy with dystonia musculorum deformans underwent an operation for removal of femoral implants and excision of the prominence at the greater trochanter of the left hip. He was found to have fat embolism syndrome at postoperative day 1 as evidenced by confusion, respiratory symptoms, chest radiograph changes, raised erythrocyte sedimentation rate, thrombocytopenia and fat in the urine and sputum.

Abnormal nuclear envelope in the cerebellar Purkinje cells and impaired motor learning in DYT11 myoclonus-dystonia mouse models.

Myoclonus-dystonia (M-D) is a movement disorder characterized by myoclonic jerks with dystonia. DYT11 M-D is caused by mutations in SGCE which codes for ɛ-sarcoglycan. SGCE is maternally imprinted and paternally expressed. Abnormal nuclear envelope has been reported in mouse models of DYT1 generalized torsion dystonia. However, it is not known whether similar alterations occur in DYT11 M-D. We developed a mouse model of DYT11 M-D using paternally inherited Sgce heterozygous knockout (Sgce KO) mice and reported that they had myoclonus and motor coordination and learning deficits in the beam-walking test. However, the specific brain regions that contribute to these phenotypes have not been identified. Since ɛ-sarcoglycan is highly expressed in the cerebellar Purkinje cells, here we examined the nuclear envelope in these cells using a transmission electron microscope and found that they are abnormal in Sgce KO mice. Our results put DYT11 M-D in a growing family of nuclear envelopathies. To analyze the effect of loss of ɛ-sarcoglycan function in the cerebellar Purkinje cells, we produced paternally inherited cerebellar Purkinje cell-specific Sgce conditional knockout (Sgce pKO) mice. Sgce pKO mice showed motor learning deficits, while they did not show abnormal nuclear envelope in the cerebellar Purkinje cells, robust motor deficits, or myoclonus. The results suggest that ɛ-sarcoglycan in the cerebellar Purkinje cells contributes to the motor learning, while loss of ɛ-sarcoglycan in other brain regions may contribute to nuclear envelope abnormality, myoclonus and motor coordination deficits.