Contrasting features between Tourette syndrome and secondary tic disorders.

Tics are rapid, recurrent, non-rhythmic movements or emitted sounds. Tics are the hallmark of Tourette syndrome (TS); however, a number of other disorders may be associated with tics, so-called secondary tic disorders (STD). We assessed clinical history and performed blinded evaluations of video-recordings from patients with TS and STD in order to identify features that may differentiate tics associated with TS vs STD. There were 156 patients with TS and 38 with STD, 21 of whom had functional (psychogenic) tics. Patients with TS were more frequently male and had a younger age at onset. Tics in TS tend to involve muscles in the cranial-cervical area more often and have greater severity and complexity than those in patients with STD. Similar findings were observed when contrasting patients with TS with patients with functional tics only. Simple phonic tics showed the greatest diagnostic accuracy for TS, compared with STD, but marked overlap in the types of tics and comorbidities was observed between patients with TS and STD. Patients with TS were more likely males, had a younger age at onset, phonic tics and motor tics affecting predominantly the head and neck area, and had a greater complexity and severity of tics than those with STD. When these features are absent a consideration should be given to the possibility of a tic disorder other than TS.

Functional gait disorders, clinical phenomenology, and classification.

BACKGROUND: Functional gait disorders (FGDs) are relatively common in patients presenting for evaluation of a functional movement disorder (FMD). The diagnosis and classification of FGDs is complex because patients may have a primary FGD or a FMD interfering with gait. METHODS: We performed a detailed evaluation of clinical information and video recordings of gait in patients diagnosed with FMDs. RESULTS: We studied a total of 153 patients with FMDs, 68% females, with a mean age at onset of 36.4 years. A primary FGD was observed in 39.2% of patients; among these patients, 13 (8.5%) had an isolated FGD (a gait disorder without other FMDs). FMDs presented in 34% of patients with otherwise normal gait. Tremor was the most common FMD appearing during gait, but dystonia was the most common FMD interfering with gait. Patients with FGD had a higher frequency of slow-hesitant gait, astasia-abasia, bouncing, wide-based gait and scissoring compared with patients with FMDs occurring during gait. Bouncing gait with knee buckling was more frequently observed in patients with isolated FGD (P = 0.017). Patients with FGDs had a trend for higher frequency of wheelchair dependency (P = 0.073) than those with FMDs interfering with gait. CONCLUSIONS: Abnormal gait may be observed as a primary FGD or in patients with other FMDs appearing during gait; both conditions are common and may cause disability.

Clinical correlations of striatal hand deformities in Parkinson's disease.

BACKGROUND: Hand deformities have been recognized since the 19th century as part of the postural abnormalities observed in Parkinson's disease (PD). However, their pathogenesis and clinical correlations are poorly understood. METHODS: We evaluated 104 hands of 52 consecutive patients with PD by high-resolution photographs taken from the radial aspect of each hand; the degree of flexion of the 2nd metacarpophalangeal (MCP) joint was measured by software. The presence of classical striatal hand deformity (CSHD) was also evaluated, defined as MCP flexion, proximal interphalangeal joint extension, and distal interphalangeal joint flexion. RESULTS: Patients with PD had a mean age of 63.3 ± 12.7 years, and 29 (56%) were male. The degree of MCP joint flexion in both hands showed moderate correlation with the MDS-UPDRS-III motor score (r = 0.518, P < 0.001), mainly related to ipsilateral rigidity and ipsilateral bradykinesia scores, and fair correlation with the Hoehn-Yahr stage. A CSHD only correlated with a younger age at onset of PD (P = 0.049). These hand deformities were not markers of dyskinesia, levodopa equivalent dose, or cognitive dysfunction. CONCLUSIONS: Metacarpophalangeal joint flexion is the most common hand deformity in PD and correlates with rigidity and bradykinesia. A CSHD was only related to a younger age at onset.

The frequency and diagnostic accuracy of hand deformities in Parkinson's disease.

Hand deformities are well-known abnormalities observed in patients with Parkinson's disease (PD). We determined the frequency and diagnostic accuracy of hand deformities in PD. We studied 44 consecutive patients with PD, 44 age- and gender-matched normal controls and 22 patients with essential tremor (ET). By means of photographs taken in both hands of all participants, the degree of metacarpophalangeal (MCP) joint flexion was quantified by software and by blinded evaluations using a semiquantitative scale from the radial aspect, we grouped hands into four grades. The presence of classical striatal hand deformity (CSHD), defined as MCP joint flexion, proximal interphalangeal joint extension and distal interphalangeal joint flexion was also evaluated. Patients with PD had a higher frequency of MCP joint flexion and CSHD compared to normal controls and patients with ET. Mean MCP joint flexion was higher in both hands in patients with PD: 20.8° vs. normal controls (3.3°-3.9°) and patients with ET (2.8°-6.3°), P = 0.001. Concordance between evaluators for MCP joint flexion was fair: κ = 0.34 (P < 0.001), but poor for CSHD: κ = 0.142-0.235 (P < 0.05). A right hand MCP joint flexion of 12.5° and left hand of 10.5°, showed similar sensitivity (0.70) and specificity (between 0.75 and 0.80) than any degree of MCP joint flexion for the diagnosis of PD. CSHD had a sensitivity (0.60-0.80) and specificity (0.78-0.98) for the diagnosis of PD. Hand deformities are commonly observed in patients with PD, they may aid in the diagnosis of PD when compared to normal controls and patients with ET.

Cerebellar disease associated with anti-glutamic acid decarboxylase antibodies: review.

Several neurological syndromes have been recognized associated to GAD antibodies. Among those disorders, cerebellar ataxia (CA) is one of the most common, along with stiff-person syndrome. Patients with GAD associated CA present with a progressive pancerebellar syndrome, with a subacute or chronic evolution, along with other neurological manifestations such as stiffness, oculomotor dysfunction, epilepsy, and cognitive dysfunction. These symptoms may be preceded by the so-called "brainstem attacks", where manifestations consistent with transient dysfunction of the brainstem may be observed. These patients frequently have extra-neurologic autoimmune manifestations such as diabetes mellitus type 1, polyendocrine autoimmune syndrome, pernicious anemia, vitiligo, etc. A proportion of patients may present with an underlying neoplasia, but the course is less aggressive than in those patients with classical paraneoplastic CA with onconeural antibodies. The diagnosis is based on the present of high serum and CSF titers of GAD antibodies, with intrathecal production of such antibodies. Treatment is aimed to decrease the immunological response with intravenous immunoglobulin, steroids, rituximab and oral immunosuppressive drugs. A subacute presentation and rapid initiation of immunotherapy seem to be the predictors of a favorable clinical response.

Clinical deterioration following middle cerebral artery hemodynamic changes after intravenous thrombolysis for acute ischemic stroke.

BACKGROUND: Little information exists regarding what occurs in the affected artery in the days after acute ischemic stroke and its impact in the outcome. We sought to determine the hemodynamic evolution and correlated this evoution with clinical outcome in stroke patients treated with intravenous thrombolysis. METHODS: Using serial transcranial Doppler ultrasound (TCD) on days 1 (TCD1), 3 to 6 (TCD2), and 7 to 10 (TCD3) after stroke, we determined the hemodynamics in the affected artery by means of the thrombolysis in brain ischemia (TIBI) score and compared this with clinical outcome (National Institutes of Health Stroke Scale [NIHSS] score) and functional outcome (modified Rankin Scale score) at discharge and at 3 months. RESULTS: Thirty-four patients were studied. There were 24 men with a mean (± SD) age of 72.9 ± 16.2 years. The mean time from stroke onset to the administration of intravenous tissue plasminogen activator was 181 ± 54.4 minutes, and the mean NIHSS score at admission was 16.9 ± 9. Hemodynamic changes were observed in 23 (68%) patients, including improvement in 17 (50%) patients and worsening in 6 (18%) patients within the first 10 days poststroke. Clinical deterioration (NIHSS ≥4 points) was timely associated with hemodynamic deterioration in 3 cases. Patients achieving full recanalization at TCD3 had better mRS scores at 3 months (4 v 3; P = .02). CONCLUSIONS: Hemodynamic changes in the affected artery occurred in about two-thirds of patients within the first 10 days after receiving intravenous thrombolysis; 18% had hemodynamic deterioration, which was associated with clinical worsening in half of these cases.

Oromandibular tics associated with Tourette syndrome.

BACKGROUND: Tourette syndrome (TS) is the most common cause of chronic tics. Patients with TS frequently manifest motor tics involving the eyes and face but oromandibular (OM) tics have been rarely studied. MATERIALS AND METHODS: We reviewed the medical records and video-recordings of 155 consecutive patients with TS in our movement disorders clinic. In addition, we studied 35 patients with classic tardive dyskinesia (TD) and compared their clinical and demographic features with those with TS. RESULTS: We identified 41 patients with OM tics (26.5%). Although patients with OM tics had a greater overall tic severity and higher frequency of.complex motor and phonic tics, in the bivariate analysis, only comorbid dystonic tics (P = 0.001), greater number of affected body parts (P = 0.012) and more frequent eye-rolling tics (P = 0.059) were included in the final regression model after controlling for other variables. When compared with patients with OM tics, patients with classic TD had more frequently masticatory movements (sensitivity, 0.86; specificity, 0.95), continuous tongue movements (sensitivity, 0.71; specificity, 1.0) and continuous OM movements (sensitivity, 0.4; specificity, 1.0). CONCLUSIONS: OM tics are common and often troublesome or even disabling symptoms in patients with TS. They may be difficult to differentiate from TD, but the latter is typically manifested by continuous orolingual and masticatory movements.

The Role of Muscle Strength in the Sit-to-Stand Task in Parkinson's Disease.

Background: Rising from a chair or the sit-to-stand (STS) task is frequently impaired in individuals with Parkinson's disease (PD). These patients commonly attribute such difficulties to weakness in the lower extremities. However, the role of muscle strength in the STS transfer task has not been fully elucidated. Objective: We aim at determining the role of muscle strength in the STS task. Methods: We studied 90 consecutive patients with PD and 52 sex- and age-matched controls. Lower limb strength was determined in both legs by clinical examination using the Medical Research Council Scale, dynamometric (leg flexion) and weighting machine (leg pressure) measures. Patients were interrogated regarding the presence of subjective lower limb weakness or allied sensations. Results: There were 20 patients (22.2%) with abnormal STS task (item 3.9 of the MDS-UPDRS-III ≥2 points). These patients had higher modified Hoehn and Yahr stage (P < 0.001) and higher total motor scores of the MDS-UPDRS(P < 0.001), compared with 70 PD patients with normal STS task. Patients with abnormal STS task endorsed lower limb weakness more frequently and had lower muscle strength in the proximal lower extremities, compared to PD patients with normal STS task and normal controls. The presence of perceived lower limb weakness increased the risk of an abnormal STS task, OR: 11.93 (95% C.I. 1.51-94.32), whereas a hip extension strength ≤9 kg/pressure also increased the risk of abnormal STS task, OR: 4.45 (95% C.I. 1.49-13.23). In the multivariate regression analysis, bradykinesia and decreased hip strength were related to abnormal STS task. Conclusions: Patients with PD and abnormal STS task complain more commonly of lower limb weakness and have decreased proximal lower limb strength compared to patients with PD and normal STS task, likely contributing to abnormalities in performing the STS task.

Dystonic motor and phonic tics in Tourette syndrome.

BACKGROUND: Dystonic tics differ from clonic tics by their slower and more sustained nature. Dystonic tics are often present in patients with Tourette syndrome (TS) and other tic-disorders. However, their phenomenology and impact on overall impairment have not been extensively studied. MATERIALS AND METHODS: We assessed clinical history and tic duration in video-recordings from patients with TS evaluated at our movement disorders clinic. Dystonic tics were defined as those lasting ≥ 1000 ms (ms). RESULTS: Of the total of 201 patients with TS, there were 156 with video-recordings suitable for tic duration analysis, of their tics, 57 (36.5%) of whom had dystonic motor tics, including 9 (5.7%) with dystonic phonic tics. Dystonic motor tics had a duration range between 1033 and 15,000 ms and dystonic phonic tics between 1132 and 17,766 ms. Patients with dystonic tics were older 24.4 vs. 16.5 years (P = 0.005) and had an older age at onset 12.9 vs. 7.2 years (P < 0.001), than patients without dystonic tics. The bivariate analysis showed an association between the presence of dystonic tics, greater tic severity and wider body distribution. The multivariate regression analysis showed a statistical association with older age at evaluation (P = 0.001), greater tic severity on video-recordings (P = 0.001) and co-occurrence with complex motor tics (P = 0.020). The presence of dystonic tics increased the risk for being considered for deep brain stimulation therapy, odds ratio: 15.7 (P = 0.002). CONCLUSION: Dystonic tics, observed in about a third of patients with TS, are associated with increased severity of TS.

Objective and self-perceived lower limb weakness in Parkinson's disease.

Background: Lower limb weakness is a long-recognized symptom in patients with Parkinson's disease (PD), described by James Parkinson in his seminal report on 'paralysis agitans'. However, little is known on the frequency, clinical correlations, and association with objective decrease in muscle strength in such patients. Objective: The objective of this study was to assess the frequency of objective and perceived lower limb weakness in patients with PD. Methods: We studied 90 consecutive patients with PD and 52 age-matched controls. We recorded clinical and demographic variables, as well as perceived weakness and allied abnormal lower limb sensations, including 'heavy legs', 'fatigued legs', and 'pain'. Symptoms consistent with restless legs syndrome were not considered. Lower limb strength was determined in both legs by means of the Medical Research Council scale, dynamometric (leg flexion) and weighting machine (leg pressure) measures. Results: Weakness and allied abnormal lower limb sensations were reported in 69% of patients with PD and 21% of healthy controls. Patients with PD had decreased leg pressure compared with healthy controls (p = 0.002). Among patients with PD, an association between perceived leg weakness (and allied sensations) and gait freezing (p = 0.001) was observed in the multivariate regression analysis; however, these variables only explained 30.4% of the variance. Moreover, PD patients with and without abnormal lower limb sensations had similar muscle strength by objective measurements. Conclusion: Perceived lower limb weakness and allied abnormal sensations are common in patients with PD. However, there is a dissociation between perceived weakness and objective muscle strength in the lower limbs. These abnormal sensations were mostly related to gait freezing but a causal association is questionable.

Self-injurious behavior in Tourette syndrome.

INTRODUCTION: Tourette syndrome (TS) is characterized by the presence of motor and phonic tics, as well as a variety of behavioral co-morbidities. Self-injurious behavior (SIB) is one of the most serious manifestations of TS, but its pathophysiology is poorly understood. METHODS: Consecutive patients with TS studied in a tertiary care center. RESULTS: We identified a total of 34 patients (16.9%) with SIB from a cohort of 201 patients with TS. Most of these patients (n = 23, 11.4%) experienced self-directed damage; while others had outward-directed (n = 7, 3.5%) or tic-related SIB (n = 4, 2%). Compared to other patients with TS, those who manifested SIB (self- and outward-directed damage) were more likely to have tics involving shoulder (P = 0.046), trunk (P = 0.006), and arm (P = 0.017); as well as dystonic tics (P = 0.016); complex motor tics (P < 0.001), copropraxia (P = 0.045), complex phonic tics (P = 0.003), higher number of phonic tics (P = 0.001), verbalizations (P = 0.001), coprolalia (P = 0.006) and obsessive compulsive disorder (OCD) (P < 0.001) as determined by bivariate analysis. In the multivariate analysis only complex motor tics (P = 0.006), obsessive-compulsive behavior (P = 0.025) and greater severity of tics (P = 0.002) showed a statistically significant association with SIB. Patients with SIB had a greater probability of being selected for deep brain stimulation (DBS) therapy by the treating clinician (P = 0.01). CONCLUSIONS: SIB is observed in about 17% of patients with TS. The presence of complex motor tics, OCD and greater severity of tics was related to the presence of SIB.

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.

Valproate-induced rest tremor and parkinsonism.

Tremor and parkinsonism are recognized side effects of valproate; however, the relationship between rest tremor and other signs of parkinsonism has not been addressed in patients taking valproate. We studied a cohort of 125 consecutive patients treated with valproate due to epilepsy or migraine, evaluated with the Fahn-Tolosa-Marin Tremor Rating Scale (FTM-TRS). A total of 14 (11.2%) patients had rest tremor (bilateral n = 10, unilateral n = 4). Patients with rest tremor had significant higher scores in the FTM-TRS (P < 0.001), but only one was diagnosed with parkinsonism. Patients may have valproate-induced parkinsonism or exacerbated motor features of Parkinson's disease by valproate. The frequency of parkinsonism was 1.6% in this cohort and of 3% in the pooled data of 717 patients from previous reports. Rest tremor is observed in 11.2% of patients treated with valproate and is related to the burden of valproate-induced tremor, rather than the presence of parkinsonism.

Intestinal Decontamination Therapy for Dyskinesia and Motor Fluctuations in Parkinson's Disease.

Parkinson's disease is neurodegenerative disorder with an initial robust response to levodopa. As the disease progresses, patients frequently develop dyskinesia and motor fluctuations, which are sometimes resistant to pharmacological therapy. In recent years, abnormalities in gut microbiota have been identified in these patients with a possible role in motor manifestations. Dysbiosis may reduce levodopa absorption leading to delayed "On" or "no-On" states. Among 84 consecutive patients with PD, we selected 14 with levodopa-induced dyskinesia and motor fluctuations with a Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part IV ≥ 8 points following a trial of pharmacological adjustment 2-3 months prior to study enrollment or adjustments in deep brain stimulation therapy. Patients received treatment with sodium phosphate enema followed by oral rifaximin and polyethylene glycol for 7 and 10 days, respectively. Evaluations between 14 to 21 days after starting treatment showed improvement in MDS-UPDRS-IV (P = 0.001), including duration (P = 0.001) and severity of dyskinesia (P = 0.003); duration of medication "Off"-state (P = 0.004); functional impact of motor fluctuations (P = 0.047) and complexity of motor fluctuations (P = 0.031); no statistical improvement was observed in "Off" dystonia (P = 0.109) and total motor scores (P = 0.430). Marked to moderate improvement in dyskinesia was observed in 57% of cases with blinded evaluation of videos. About 80% of patients perceived moderate to robust improvement at follow-up. A therapeutic strategy aimed at decontamination of intestines showed benefit in motor fluctuations and dyskinesia. Further studies should confirm and clarify the mechanism of improvement observed in these patients.

Functional (Psychogenic) Movement Disorders Presenting During Sleep.

Background: Functional (psychogenic) movement disorders are involuntary movements that seems to originate from activation of voluntary motor pathways in the brain. The movements typically present during the waking hours with variable frequency. Case presentation: We present the case of a 24-year-old woman with FMDs during the waking state, but also during stages 1 and 2 of non-REM sleep and REM sleep, recorded with polysomnography. Such movements caused arousal leading to excessive daytime sleepiness and fatigue. Conclusions: FMDs may disrupt sleep causing day time somnolence, adding morbidity to the disorder.

The Link between Gut Dysbiosis and Neuroinflammation in Parkinson's Disease.

Parkinson's disease (PD) is the second most common neurodegenerative disorder. Despite its high frequency the etiology is still unclear; several lines of evidence show that an inflammatory process is implicated in the pathogenesis of this disorder; where activation of brain microglia plays a central role in the damage of dopaminergic neurons of the substantia nigra. Such inflammation has been attributed to the toxic effect of aggregated α-synuclein; however, evidence also implicates an altered gut microbiota (dysbiosis) through the systemic release of endotoxins such as lipopolysaccharide and other metabolic products. This exposure may be enhanced by increased permeability of the intestinal ("leaky gut") and the blood brain barrier; enhancing the entrance of microbiota-produced substances into the central nervous system. In this manuscript, we explore the evidence from clinical and basic science implicating microglia activation by gut dysbiosis and how this phenomenon may impact in the symptomatology and progression of PD.

Anti-Gravity Treadmill Training for Freezing of Gait in Parkinson's Disease.

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor impairment. Freezing of gait, impaired mobility and falls are common problems in these patients. We aimed to evaluate the effect of a novel therapy for these patients. METHODS: We studied patients with moderate to severe freezing of gait who underwent antigravity treadmill training twice a week for 4 consecutive weeks with 50% reduction of body weight. RESULTS: We enrolled 26 consecutive patients with PD, 19 completed the study. There were 10 males; mean age at evaluation was 72.7 ± 10.1 years. Compared to baseline, patients showed improvement in the Freezing of Gait Questionnaire (p = 0.001); and a mean reduction of 7 s in the Timed Up & Go (TUG) test (p = 0.004). Moderate or significant improvement in gait was reported by 84% of patients. CONCLUSIONS: Antigravity treadmill training improved freezing of gait and mobility in patients with PD.

Vertical nystagmus associated with glutamic acid decarboxylase antibodies responding to cyclophosphamide.

Several neurological disorders have been described in patients with autoimmunity associated with GAD antibodies. Among these disorders, nystagmus and oculomotor dysfunction are increasingly recognized, although they have been rarely reported isolated or as the main manifestation of anti-GAD autoimmunity. Moreover, therapeutic approaches for such patients are unclear. Here we present a 44-year-old man with disabling oscillopsia secondary to downbeat nystagmus, abnormal saccades, ocular pursuit and optokinetic nystagmus, as well as mild gait ataxia and cerebellar atrophy associated with high serum GAD antibodies with intrathecal secretion of such antibodies. The patient did not have clinical benefit with plasma exchange, but had a robust symptomatic improvement with cyclophosphamide. We discuss the possible pathogenic role of GAD antibodies in nystagmus and the role of immunotherapy in these patients.

The clinical features and functional impact of valproate-induced tremor.

BACKGROUND: Tremor is a known side-effect of anticonvulsants, particularly of valproate. However, there is a dearth of information regarding detailed clinical features and functional impact of valproate-induced tremor. METHODS: We studied a cohort of patients treated with anticonvulsants for neurological disorders, through blinded evaluations using the Clinical Rating Scale for Tremor (CRST); we compared the frequency, severity and functional impact of drug-induced tremor between patients treated with valproate and those treated with other anticonvulsants. RESULTS: From a cohort of 218 consecutive patients, 171 were fully evaluated; 118 patients were taking valproate alone or combined with other anticonvulsants and 53 patients were taking other anticonvulsants. Mean age (±SD) at evaluation of the cohort was 32 ± 13 years, females represented 55.6% of cases. Tremor was more frequently observed in patients taking valproate particularly postural upper limb tremor: 49% vs. 15% (right-side) (P < 0.001) and 48.3% vs. 13.2% (left-side), (P < 0.001); had a higher total CRST score: 12.14 vs. 3.06 (P < 0.001), and required more frequently treatment for drug-induced tremor: 23.7% vs. 5.6% (P=0.005) compared with patients taking other anticonvulsants. Among 118 patients taking valproate, women had a higher total CRST score compared with men: 14.54 ± 14.9 vs. 9.56 ± 9.55 (P=0.034). A weak correlation between the total CRST score, dose per Kg of valproate and serum levels of valproate were observed. CONCLUSIONS: Tremor is frequently observed in patients taking valproate and is severe enough to require treatment in about 24% of cases.