José Fidel Baizabal-Carvallo

The safety and efficacy of thalamic deep brain stimulation in essential tremor: 10 years and beyond

Background Deep brain stimulation (DBS) has proven to be a safe and effective therapy for refractory essential tremor, but information regarding long-term outcomes is lacking. Objectives We aimed to assess the long-term safety and efficacy of DBS in patients with essential tremor. Methods Patients treated with DBS for essential tremor for at least 8 years were evaluated in the ‘on’ and ‘off’ state using the Fahn–Tolosa–Marin tremor rating scale, and their medical records were reviewed to assess complications related to this therapy. Results We studied 13 patients (7 men): median age at evaluation 79 years (range 47–88), median age at electrode implantation 68 years (range 37–78) and mean time since electrode implantation 132.54±15.3 months (range 114–164). The difference between the ‘off’ and ‘on’ state on the motor items of the tremor rating scale was 41.9% (58.62 vs 34.08, p<0.001) in the non-blinded and 37.2% (56.07 vs 35.23, p<0.001) in the blinded rating. DBS provided a functional improvement of 31.7% in the ‘on’ state (15.07 vs 22.07, p<0.001). A total non-blinded improvement in the tremor rating scale of 39% was observed in the ‘on’ state (49.15 vs 80.69, p<0.001). Dysarthria and disequilibrium were common in patients with bilateral stimulation. A DBS-related surgery (electrode revision or internal pulse generator exchange) was necessary on average every 47.9 months to continue with the DBS therapy. Conclusions Thalamic DBS is a safe and effective therapy in patients with essential tremor followed for up to 13 years.

The spectrum of movement disorders in children with anti-NMDA receptor encephalitis.

Movement disorders are frequent but difficult to characterize in patients with anti‐N‐methyl‐d‐aspartate receptor (NMDAR) encephalitis.

Movement disorders in autoimmune diseases

Movement disorders have been known to be associated with a variety of autoimmune diseases, including Sydenhams chorea, pediatric autoimmune neuropsychiatric disorders associated with streptococcus, systemic lupus erythematosus, antiphospholipid syndrome, gluten sensitivity, paraneoplastic and autoimmune encephalopathies. Tremors, dystonia, chorea, ballism, myoclonus, parkinsonism, and ataxia may be the initial and even the only presentation of these autoimmune diseases. Although antibodies directed against various cellular components of the central nervous system have been implicated, the pathogenic mechanisms of these autoimmune movement disorders have not yet been fully elucidated. Clinical recognition of these autoimmune movement disorders is critically important as many improve with immunotherapy or dietary modifications, particularly when diagnosed early. We discuss here the clinical features, pathogenic mechanisms, and treatments of movement disorders associated with autoimmune diseases, based on our own experience and on a systematic review of the literature.

Posterior reversible encephalopathy syndrome as a complication of acute lupus activity

OBJECTIVES We aimed to describe the clinical and imaging characteristics; associated risk factors and neurological outcome of posterior reversible encephalopathy syndrome (PRES) in patients with systemic lupus erythematosus (SLE). METHODS From October 2001 to January 2007, we identified patients with SLE and the criteria for PRES in our institution, which is a tertiary-care referral center for patients with SLE; the patients were evaluated at baseline and followed to determine the clinical outcome. RESULTS We identified 22 episodes of PRES in 21 patients; 20 (95.2%) were women, mean age of onset was 24.9+/-8.6 years, all patients had high systemic activity (SLEDAI scores from 12 to 39). Acute hypertension was observed in 18 episodes (81.8%), and renal failure in 16 (72.7%); only 3 patients were on cyclophosphamide at the time of the onset of PRES. Persistent neurological deficit was observed in 2 cases; one patient died during the acute episode. CONCLUSIONS PRES is a central nervous system syndrome that is observed in SLE patients. It was associated mainly to high systemic activity, acute hypertension, and renal failure. Although reversibility is common, residual neurological damage may be observed.

Movement disorders in systemic lupus erythematosus and the antiphospholipid syndrome

Movement disorders (MDs), particularly chorea, may be the presenting neurological complication of systemic lupus erythematosus (SLE) and the antiphospholipid syndrome (APS), but the association is not often initially recognized. Current evidence suggests an autoimmune mechanism related to antiphospholipid antibodies in these two conditions, although the antigenic target within the central nervous system has not yet been identified. Based on a comprehensive review of the literature, this article summarizes the current knowledge on MDs in SLE and APS. A high index of suspicion is required to make an early diagnosis and initiate appropriate treatment to provide symptomatic relief and to prevent other systemic complications related to the autoimmune process.

The clinical features of psychogenic movement disorders resembling tics

Background Psychogenic movement disorders (PMDs) may be difficult to differentiate from organic abnormal movements. Methods We aimed to characterise the prevalence and clinical features of PMDs resembling tics during the last 3.5 years in our centre. Results We studied 9 patients (five females) with psychogenic tics representing 4.9% of all 184 patients first evaluated for a PMD during the study period. The mean age at onset was 34.1 years. Lack of premonitory sensations, absence childhood and family history of tics, inability to suppress the movements and coexistence with other PMDs and pseudoseizures were common in our patients. Compared with 273 patients with Tourette syndrome, those with PMDs resembling tics were older: 36.3 versus 18.7 years (p=0.014) at presentation and more frequently female (p=0.030). Conclusions Movements resembling tics are observed in a small proportion of patients with PMDs. Clinical features can help to differentiate them from organic tics.

Stiff-person syndrome: insights into a complex autoimmune disorder

Stiff-person syndrome (SPS) is characterised by progressive rigidity and muscle spasms affecting the axial and limb muscles. Since its initial description in 1956, marked progress has been made in the clinical characterisation, understanding of pathogenesis and therapy of this disorder. SPS can be classified according to the clinical presentation into classic SPS and SPS variants: focal or segmental-SPS, jerking-SPS and progressive encephalomyelitis with rigidity and myoclonus. Most patients with SPS have antibodies directed against the glutamic acid decarboxylase, the rate-limiting enzyme for the production of the inhibitory neurotransmitter γ-aminobutyric acid (GABA). Antibodies directed against GABAA receptor-associated protein, and the glycine-α1 receptor can also be observed. Paraneoplastic SPS is commonly associated with antiamphiphysin antibodies and breast cancer. Treatment of SPS with drugs that increase the GABAergic tone combined with immunotherapy can improve the neurological manifestations of these patients. The prognosis, however, is unpredictable and spontaneous remissions are unlikely.

Convergence spasm in conversion disorders: prevalence in psychogenic and other movement disorders compared with controls

Background Convergence spasm refers to transient ocular convergence, miosis and accommodation associated with disconjugate gaze mimicking abducens palsy. While it may be a manifestation of brainstem pathology, this sign is often associated with conversion (somatisation) disorders and, if unrecognised as a sign of a psychogenic disorder, it may lead to unnecessary and occasionally invasive evaluation. Methods To better characterise this neuro-ophthalmologic sign, 36 subjects were studied, 13 with psychogenic movement disorders, 11 with organic movement disorders and 12 normal controls. Patients were recorded during a manoeuvre to elicit convergence spasm and the videotapes were rated by two blinded raters on a scale of 0=normal, 1=mild convergence spasm and 2=marked convergence spasm. Results Convergence spasm was present in 9/13 (69%) psychogenic movement disorders cases, 4/11 (36%) non-psychogenic movement disorders cases and 4/12 (33%) controls (p=0.049 when psychogenic vs non-psychogenic disorders or controls were compared). Inter-rater reliability analysis of the presence (rating 1 or 2) versus absence (rating 0) showed good agreement (27/36 or 75%; kappa 0.491, SE 0.141, p=0.002). Analysis for the presence of marked convergence spasm (rating 2) yielded agreement in 32/36 (88.9%) examinations (kappa 0.652, SE 0.154, p<0.001) with a specificity of 87% (sensitivity 15%). Conclusion Convergence spasm may provide benefit in the clinical examination of psychogenic movement disorders patients.

Parkinsonism, movement disorders and genetics in frontotemporal dementia

Frontotemporal dementia (FTD) refers to a group of clinically and genetically heterogeneous neurodegenerative disorders that are a common cause of adult-onset behavioural and cognitive impairment. FTD often presents in combination with various hyperkinetic or hypokinetic movement disorders, and evidence suggests that various genetic mutations underlie these different presentations. Here, we review the known syndromatic–genetic correlations in FTD. Although no direct genotype–phenotype correlations have been identified, mutations in multiple genes have been associated with various presentations. Mutations in the genes that encode microtubule-associated protein tau (MAPT) and progranulin (PGRN) can manifest as symmetrical parkinsonism, including the phenotypes of Richardson syndrome and corticobasal syndrome (CBS). Expansions in the C9orf72 gene are most frequently associated with familial FTD, typically combined with motor neuron disease, but other manifestations, such as symmetrical parkinsonism, CBS and multiple system atrophy-like presentations, have been described in patients with these mutations. Less common gene mutations, such as those in TARDBP, CHMP2B, VCP, FUS and TREM2, can also present as atypical parkinsonism. The most common hyperkinetic movement disorders in FTD are motor and vocal stereotypies, which have been observed in up to 78% of patients with autopsy-proven FTD. Other hyperkinetic movements, such as chorea, orofacial dyskinesias, myoclonus and dystonia, are also observed in some patients with FTD.

Chorea in systemic lupus erythematosus.

Background:Chorea is recognized as one of the neurologic manifestations of systemic lupus erythematosus (SLE). Most reports show an association between chorea and antiphospholipid (aPL) antibodies in SLE patients. Objectives:The objective of this study was to describe the association of aPL antibodies with lupus chorea and its possible role in the pathogenesis of chorea. Methods:We made a retrospective review of all cases of lupus chorea between 1989 and 2007 in a tertiary care center in Mexico City. Results:We found 7 episodes of chorea in 5 patients with SLE. In 2 patients (3 episodes), chorea was associated with cerebral ischemia; one of these cases had positive anticardiolipin (aCL) immunoglobulin G (IgG) antibodies, whereas the other was diagnosed as having vascular lipohyalinosis as the probable cause of cerebral ischemia. In 3 patients (4 episodes), an immune-mediated mechanism was suspected; these cases had negative aPL at the onset of chorea, but IgM aCL antibodies became positive later. Conclusions:In most episodes, chorea seems to be immunologically mediated and was associated with a later appearance of IgM aCL antibodies. Chorea in patients with lupus may also be caused by cerebral ischemia, and in some cases, it may be associated with IgG aCL antibodies.