Lucia Angelini

Stimulation of the globus pallidus internus for childhood-onset dystonia

We report the results of deep brain stimulation (DBS) of the globus pallidus internus (GPi) in 12 patients with childhood‐onset generalized dystonia refractory to medication, including 3 patients with status dystonicus. There were 8 patients who had DYT1‐negative primary dystonia, 1 had DYT1‐positive dystonia, and 3 had symptomatic dystonia. Stimulation was effective in all but 1 patient. Dystonic postures and movements of the axis and limbs responded to DBS to a greater extent than oromandibular dystonia and fixed dystonic postures. These findings provide further evidence that pallidal stimulation is an effective treatment for intractable childhood‐onset dystonia, including status dystonicus, and together with previous findings, suggest that it should be considered the treatment of choice for these conditions.

Infantile neuroaxonal dystrophy Clinical spectrum and diagnostic criteria

Objective: To present clinical, neurophysiologic, and neuroradiologic findings in 13 patients with infantile neuroaxonal dystrophy (INAD), focusing on aspects that assist early diagnosis. Background: Clinicopathologic diagnostic criteria for INAD were delineated by Aicardi and Castelein in 1979, but atypical cases are reported frequently and little is known of the diagnostic utility of MRI. Methods: The authors reviewed the clinical, neurophysiologic, and MRI findings of 13 patients who met the diagnostic criteria for INAD. Results: Symptoms onset was between 6 months and 2 years of age. In nine patients the clinical course was typical, with rapid motor and mental deterioration; in four patients progression was slower and the clinical picture was different. Electromyographic (EMG) signs of chronic denervation, fast rhythms on EEG and abnormal visual evoked potentials were observed in all patients during the disease course. Cerebellar atrophy with signal hyperintensity in the cerebellar cortex on T2-weighted images were the most characteristic MRI findings; hypointensity in the pallida and substantia nigra was also observed in two patients. α-N-acetyl-galactosaminidase activity on leukocytes was normal in the 10 patients tested. Conclusions: EMG and MRI abnormalities are the earliest and most suggestive signs of INAD, which has a clinical and radiologic spectrum that is broader than reported previously.

Life-threatening dystonia–dyskinesias in a child: Successful treatment with bilateral pallidal stimulation

We report a 13‐year‐old boy who developed severe, refractory dystonia–dyskinesias as an abrupt worsening of a previously nonprogressive movement disorder. The movements became continuous, requiring artificial respiration and continuous sedation in the intensive‐care unit. Various drugs and drug combinations failed to achieve control. The child was then treated successfully with bilateral pallidal (GPi) stimulation as shown in the videotape. Four months later and without medication, the boy regained autonomous gait and audible speech; his neurologic condition continues to improve.

Frequency of DYT1 mutation in early onset primary dystonia in Italian patients

Thirty Italian patients with sporadic, early‐onset, primary dystonia were screened for the DYT1 mutation. Five patients were positive (mean age at onset, 8 years); two had the typical phenotype, two a generalised dystonia also involving the cranial muscles, and one a segmental dystonia. In the other 25 patients (mean age at onset, 7.7 years), dystonia was generalised in 22 patients and remained segmental in three. Our results indicate the role of DYT1 mutation in Italian patients and confirm clinical and genetic heterogeneity of early‐onset primary dystonia.

Neonatal dopa-responsive extrapyramidal syndrome in twins with recessive GTPCH deficiency

The authors report two twin sisters, age 15 years, with recessive GTP cyclohydrolase deficiency, who presented with neonatal onset of rigidity, tremor, and dystonia but with no other symptoms suggestive of a diffuse CNS involvement. The plasma phenylalanine levels were normal. Treatment with l-dopa/carbidopa, started at age 1 year, was associated with sustained recovery from all neurologic signs. The patients were homozygous for a new recessive mutation in the GHI gene.

Brainstem encephalitis resulting from Epstein-Barr virus mimicking an infiltrating tumor in a child

A case of a child with subacute neurologic features and imaging findings consistent with a brainstem encephalitis that was discovered to be related to a primary central nervous system infection caused by Epstein-Barr virus is presented. A brainstem tumor was initially suspected, but a correct diagnosis was formulated on the basis of the favorable clinical course and the detection of positive Epstein-Barr virus serology. In contrast to a prompt recovery of neurologic signs the neuroimaging alterations persisted for a longer time. The present report emphasizes the possible role of Epstein-Barr virus in the pathogenesis of infectious neurologic disorders in childhood, underlining the unusual presentation of a brainstem encephalitis, and considers the discrepancy between the course of neurologic features and the evolution of imaging alterations.

Paroxysmal dyskinesias in childhood

We report on clinical features of a large series of patients with paroxysmal dyskinesias. Fourteen patients had paroxysmal kinesigenic dyskinesia, with a mean age at onset of 7.1 years. In thirteen children the condition was idiopathic and nine of them had a positive family history; the remaining one had a Chiari malformation. Response to antiepileptic drugs was good in 60% of the treated patients. Six children had paroxysmal non-kinesigenic dyskinesia, with a mean age at onset of 8.1 years. Five children were symptomatic because of cerebral palsy (two patients), basal ganglia stroke (one patient), and acute inflammatory encephalopathy (one patient); the remaining patients condition was familial with autosomal-dominant mode of inheritance. Response to medical treatment was unsuccessful contrasting with paroxysmal kinesigenic dyskinesia. Six children had paroxysmal exercise-induced dyskinesia, with a mean age at onset of 5 years. Their condition was idiopathic, with a positive family history in four. Two of these patients had also rolandic epilepsy and writers cramp, and the syndrome had been previously mapped to chromosome 16. Although there have been great advances in the genetics of paroxysmal dyskinesias in which an ion channel dysfunction has been hypothesized, the diagnosis is still based on clinical grounds. The precise classification of the patients with paroxysmal dyskinesias is important for therapeutic decisions.

Myoclonic dystonia as unique presentation of isolated vitamin E deficiency in a young patient

We describe a young patient affected by vitamin E deficiency with mutation in the tocopherol tranfer protein alleles and the unique presentation as myoclonic dystonia, which was practically the only symptom for 6 years before ataxia became evident. Vitamin E supplementation markedly improved both symptoms. This unusual clinical phenotype must be considered, because isolated vitamin E deficiency is eminently treatable.

Acquired hemidystonia in childhood: A clinical and neuroradiological study of thirteen patients

A retrospective study of 13 patients (4 males/9 females) with acquired hemidystonia in childhood is reported. The mean age of onset of hemidystonia was 6.4 years (range 1-13.4 years); the mean duration of dystonia at the time of last follow-up was 11.4 years (range 3.6-23 years). Hemidystonia was caused by ischemic infarction in 9 patients and was attributed to perinatal trauma in 1; in 4 of the 9 patients with stroke and in the remaining 3 patients laboratory investigations were suggestive of primary antiphospholipid syndrome. Eleven of the 13 patients had delayed onset of dystonia: between 1 month and 8.9 years (mean 3.4 years). Ten patients had neuroradiological evidence of contralateral basal ganglia damage. A history of hemiparesis and evidence of striatal damage on CT or MRI were important risk factors for the development of dystonia. Response to medical treatment (trihexyphenidyl dose as high as 40 mg daily) in 5 patients was disappointing; 4 of the 5 patients who underwent functional stereotaxic operations were improved, but dystonia was still present at the end of the follow-up. Our study provides additional evidence that lesions of the striatum may induce dystonia, supporting the theory of striatopallido-thalamic disconnection. Furthermore, our results indicate that the occurrence of delayed dystonia must be considered in the diagnostic approach to childhood-onset dystonia.

Primary antiphospholipid syndrome and neurologic events

The occurrence of lupus anticoagulant and anticardiolipin antibodies was demonstrated in a girl affected by recurrent episodes of visual disturbances, with ophthalmologic evidence of visual impairment and sometimes accompanied by migraine. Systemic lupus erythematosus was excluded on the basis of both clinical and serologic criteria and the diagnosis of primary antiphospholipid syndrome was made. Vascular pathogenesis was suggested by the characteristic symptoms. The serologic demonstration of antiphospholipid antibodies made it possible to relate the illness to an immune-mediated thrombotic tendency. This patient demonstrated that the diagnosis of primary antiphospholipid syndrome must always be considered in focal cerebral or retinal ischemia in childhood.