Antiseizure Drugs and Movement Disorders.

The relationship between antiseizure drugs and movement disorders is complex and not adequately reviewed so far. Antiseizure drugs as a treatment for tremor and other entities such as myoclonus and restless leg syndrome is the most common scenario, although the scientific evidence supporting their use is variable. However, antiseizure drugs also represent a potential cause of iatrogenic movement disorders, with parkinsonism and tremor the most common disorders. Many other antiseizure drug-induced movement disorders are possible and not always correctly identified. This review was conducted by searching for all the possible combinations between 15 movement disorders (excluding ataxia) and 24 antiseizure drugs. The main objective was to describe the movement disorders treated and worsened or induced by antiseizure drugs. We also summarized the proposed mechanisms and risk factors involved in the complex interaction between antiseizure drugs and movement disorders. Antiseizure drugs mainly used to treat movement disorders are clonazepam, gabapentin, lacosamide, levetiracetam, oxcarbazepine, perampanel, phenobarbital, pregabalin, primidone, topiramate, and zonisamide. Antiseizure drugs that worsen or induce movement disorders are cenobamate, ethosuximide, felbamate, lamotrigine, phenytoin, tiagabine, and vigabatrin. Antiseizure drugs with a variable effect on movement disorders are carbamazepine and valproate while no effect on movement disorders has been reported for brivaracetam, eslicarbazepine, lacosamide, and stiripentol. Although little information is available on the adverse effects or benefits on movement disorders of newer antiseizure drugs (such as brivaracetam, cenobamate, eslicarbazepine, lacosamide, and rufinamide), the evidence collected in this review should guide the choice of antiseizure drugs in patients with concomitant epilepsy and movement disorders. Finally, these notions can lead to a better understanding of the mechanisms involved in the pathophysiology and treatments of movement disorders.

Yerbamate Tea Consumption: A Protective Factor in Parkinson Disease.

INTRODUCTION: Little is known about the association between Yerbamate (YMT) tea consumption and Parkinson disease (PD). We determined whether there was an association between YMT tea consumption and PD. METHODS: We conducted a multicenter case-control study in 3 countries (Argentina, Paraguay, and Uruguay). We applied a structured questionnaire about YMT tea consumption history. The survey also included information about factors previously associated with a decreased and increased risk of PD, apart from medical and demographic factors. Odds ratios and 95% confidence intervals were calculated using multivariate unconditional binary logistic regression analysis. RESULTS: We included 215 cases and 219 controls. The mean age of the cases was 65.6 ± 10.5 years and that of controls was 63.1 ± 10.5 years (P < 0.02). Years of YMT tea consumption, number of liters drunk per day, and amount of YMT used for preparing the infusion were similar between cases and controls (P > 0.05), but not the number of times the YMT was added into the container (P = 0.003) and the YMT tea concentration per serving (P = 0.02). The multivariate analysis showed that YMT tea concentration per serving lowered the risk for PD, independent of potential confounders (odds ratio, 0.62; 95% confidence interval, 0.47-0.84). CONCLUSIONS: This multicenter study highlights the association between an environmental factor, the YMT tea drinking, and PD. Although more evidence from longitudinal studies is needed, the results obtained here points toward a protective effect of the YMT tea concentration per serving on PD.

Spastic Paraplegia Type 7 and Movement Disorders: Beyond the Spastic Paraplegia.

Background: Spastic paraplegia type 7 (SPG7) mutations can present either as a pure form or a complex phenotype with movement disorders. Objective: Describe the main features of subjects with SPG7 mutations associated with movement disorders. Methods: We analyzed the clinical and paraclinical information of subjects with SPG7 mutations associated with movement disorders. Results: Sixteen affected subjects from 11 families were identified. Male sex predominated (10 of 16) and the mean age at onset was 41.25 ± 16.1 years. A cerebellar syndrome was the most frequent clinical movement disorder phenotype (7 of 16); however, parkinsonism (2 of 16), dystonia (1 of 16), and mixed phenotypes between them were also seen. The "ears of the lynx" sign was found in four subjects. A total of nine SPG7 variants were found, of which the most frequent was the c.1529C > T (p.Ala510Val). Conclusion: This case series expands the motor phenotype associated with SPG7 mutations. Clinicians must consider this entity in single or familial cases with combined movement disorders.

Single-Trajectory Multiple-Target Deep Brain Stimulation for Parkinsonian Mobility and Cognition.

BACKGROUND: Deep brain stimulation (DBS) of the nucleus basalis of Meynert (NBM) is an emerging target to potentially treat cognitive dysfunction. OBJECTIVES: The aim of this study is to achieve feasibility and safety of globus pallidus pars interna (GPi) and NBM DBS in advanced PD with cognitive impairment. METHODS: We performed a phase-II double-blind crossover pilot trial in six participants to assess safety and cognitive measures, the acute effect of NBM stimulation on attention, motor and neuropsychological data at one year, and neuroimaging biomarkers of NBM stimulation. RESULTS: NBM DBS was well tolerated but did not improve cognition. GPi DBS improved dyskinesia and motor fluctuations (P = 0.04) at one year. NBM stimulation was associated with reduced right frontal and parietal glucose metabolism (P < 0.01) and increased low- and high-frequency power and functional connectivity. Volume of tissue activated in the left NBM was associated with stable cognition (P < 0.05). CONCLUSIONS: Simultaneous GPi and NBM stimulation is safe and improves motor complications. NBM stimulation altered neuroimaging biomarkers but without lasting cognitive improvement. © 2021 International Parkinson and Movement Disorder Society.

Adherence to treatment in Parkinson's disease: A multicenter exploratory study with patients from six Latin American countries.

BACKGROUND: Adherence to treatment in Parkinson's disease (PD) is compromised due to the need for multiple therapies, comorbidities related to aging, and the complexity of therapeutic schemes. In the present study, we aimed to explore adherence to treatment in groups of PD patients from six Latin-American (LA) countries and identify its associated demographic and clinical parameters. METHODS: A multicenter, cross-sectional, exploratory study was conducted from September 2016 to March 2017. Treatment adherence was assessed using the simplified medication adherence questionnaire (SMAQ), applied to patients and caregivers. Sociodemographic and clinical variables (MDS-UPDRS Part III-IV, MMSE, Beck Depression Inventory-II (BDI-II)) were recorded. RESULTS: Eight hundred patients from six LA countries were evaluated. Nonadherence was reported in 58.25% of the population, according to patients. The most frequent issues were forgetfulness and correct timing of doses. A high level of agreement in adherence prevalence and most SMAQ items were observed between patients and their caregivers. The nonadherent population had a significantly higher proportion of unemployment, free access to medication, troublesome dyskinesias and off-periods, lesser years of education, and worse motor, cognitive, and mood scores. In multiple logistic and linear regression analyses, MDS-UPDRS Part III, BDI-II, gender, free access to medication, treatment with dopamine agonists alone, years of education, excessive concerns about adverse effects, and beliefs about being well-treated remained significant contributors to adherence measures. CONCLUSION: Educational strategies, greater involvement of PD patients in decision-making, and consideration of their beliefs and values might be of great need to improve medication adherence in this PD population.

Aripiprazole in Meige Syndrome: Clinical Response and Implications for Treatment Development.

INTRODUCTION: Meige syndrome is a segmental form of dystonia where botulinum toxins are the preferred treatment option. However, its invasive nature, treatment costs, partial responsiveness, and benefit duration are some of their limitations. METHODS: Six consecutive subjects with Meige syndrome were treated only with aripiprazole. RESULTS: A dramatic response was obtained in all subjects during the first weeks of treatment. Aripiprazole mean ± SD daily dose was 7.9 ± 3.6 mg. Three subjects developed parkinsonism related to aripiprazole treatment; the former improved after reducing the dosage, without significant worsening of cranial dystonia. After a mean ± SD follow-up of 2.0 ± 0.7 years, clinical benefit persists over time, with a mean percentage reduction of Unified Dystonia Rating Score of 75.6% ± 8.4%. CONCLUSIONS: Aripiprazole should be considered as an alternative treatment option among subjects with Meige syndrome, especially in those refractory to botulinum toxin injections. The clinical response shown in our patients may lead to treatment development.

Non-Motor Fluctuations in Parkinson's Disease: Validation of the Non-Motor Fluctuation Assessment Questionnaire.

BACKGROUND: In patients with Parkinson's disease (PD), sleep, mood, cognitive, autonomic, and other non-motor symptoms may fluctuate in a manner similar to motor symptoms. OBJECTIVES: To validate a final version of a patient-rated questionnaire that captures the presence and severity of non-motor fluctuations in levodopa-treated PD patients (NoMoFA). METHODS: We recruited PD subjects from five movement disorders centers across the US and Canada. We assessed the internal consistency, floor and ceiling effects, test-retest reliability, and concurrent validity of NoMoFA. Classical test theory and item response theory methods informed item reduction and Delphi process yielded a final questionnaire. RESULTS: Two hundred subjects and their care-partners participated in the study (age: 66.4 ± 9.6 years; disease duration: 9 ± 5.5 years; median Hoehn and Yahr [H&Y] OFF: 3 [range 1-5]; mean Unified Parkinson's Disease Rating Scale (UPDRS) III ON score: 27.4 ± 14.9). Acceptability of the scale was adequate. There were floor effects in 8/28 items. Cronbach's alpha was 0.894. While eight items had "item-to-total" correlations below the cutoff of 0.4, removing these items did not improve Cronbach's alpha. Test-retest reliability was acceptable (intraclass correlation coefficient [ICC] 0.73; 95% confidence interval, 0.64-0.80). Concurrent validity was adequate with all Spearman's rho values comparing NoMoFA score to other measures of parkinsonian severity showing significance and in the expected direction. A final Delphi panel eliminated one item to avoid redundancy. CONCLUSIONS: The final 27-item self-administered NoMoFA is a valid and reliable questionnaire, capturing both static and fluctuating non-motor symptoms in PD. © 2021 International Parkinson and Movement Disorder Society.

Generalized Dystonia and Paroxysmal Dystonic Attacks due to a Novel ATP1A3 Variant.

Background: Paroxysmal movement disorders are a heterogeneous group of neurological diseases, better understood in recent years thanks to widely available genetic testing. Case report: A pair of monozygotic twins with dystonia and paroxysmal attacks, resembling paroxysmal non-kinesigenic dyskinesias, due to a novel ATP1A3 variant are reported. The complete resolution of their paroxysms was achieved using levodopa and deep brain stimulation of the internal globus pallidus. Improvement of interictal dystonia was also achieved with this therapy. Discussion: Paroxysmal worsening of movement disorders should be suspected as part of the ATP1A3 spectrum. Treatment outcome might be predicted based on the phenotype.

The Spectrum of Acute Disseminated Encephalomyelitis and Mild Encephalopathy with Reversible Splenial Lesion.

BACKGROUND: Acute disseminated encephalomyelitis and mild encephalopathy with reversible splenial lesion are autoimmune demyelinating disorders of central nervous system. Diagnosis remains clinical, aided by neuroimaging confirmation and excluding other causes. In the absence of a biological marker, the diagnosis of these entities based on clinical and imaging criteria could overlap. METHODS: We describe a 22-year-old woman developing mild neurological signs after an upper tract infection, a brain magnetic resonance image revealed confluent, symmetrical white matter lesions with corpus callosum involvement; after extensive ancillary testing that ruled out secondary causes we concluded that this subject had a post infectious encephalitis sharing clinical and imaging criteria for acute disseminated encephalomyelitis. However, mild encephalopathy with reversible splenial lesion could be an alternate diagnosis for this subject. Treatment with methylprednisolone completely solved both the clinical and image abnormalities without relapsing for more than 3 years of follow-up. CONCLUSION: Both acute disseminated encephalomyelitis and mild encephalopathy with reversible splenial lesion share clinical and radiological features. A biological marker is needed to differentiate among these entities, since overlap is seen according to current criteria.

Beyond dystonia and ataxia: Expanding the phenotype of SQSTM1 mutations.

BACKGROUND: Homozygous sequestomosome-1 gene mutations have been recently linked to neurodegeneration with dystonia, ataxia and gaze palsy. Seven affected families were identified thus far. OBJECTIVE: To describe four new cases with additional phenotypical features. RESULTS: Four affected patients from two unrelated families were identified. Two compound heterozygous variants of the gene (c.257_259delins35 and c.301+1G > T) were found in one family (cases 1 and 2), and homozygous c.823_824delAG variant was identified in cases 3 and 4. In addition to the previously described syndrome characterized by cerebellar ataxia, dystonia, choreoathetosis, cognitive impairment and gaze palsy, two subjects presented with iridoplegia. Furthermore, we report dysautonomic features such as orthostatic hypotension and sudomotor dysfunction, along with other non-motor symptoms. CONCLUSIONS: We expand the phenotype of dystonia caused by Sequestomosome-1 gene by identifying dysautonomic features along with other non-motor symptoms.

Superficial siderosis misdiagnosed as idiopathic bilateral neurosensorial deafness.

Superficial siderosis (SS) is a rare condition resulting from different sources of bleeding into the subpial space. The most common symptoms are: hypoacusia, ataxia, incontinence, dementia and parkinsonism. Since several neurodegenerative disorders may present with same clinical features, SS is often misdiagnosed. Here we present a case of SS misdiagnosed as idiopathic bilateral neurosensorial deafness.

Allergy to Carbidopa.

BACKGROUND: D-Decarboxylase inhibitors, such as carbidopa or benserazide, have been used as adjunct therapy in Parkinson disease shortly after levodopa synthesis in the 1960s. These compounds increase intracerebral drug concentration and decrease adverse effects by blocking peripheral conversion to dopamine. Skin rash as part of an allergic reaction was previously described in subjects who were using levodopa in combination with carbidopa or benserazide; however, etiology was never clear. Allergic reactions to carbidopa have not previously been reported. METHODS: We report a case of a 77-year-old woman with a diagnosis of idiopathic Parkinson disease, who developed autonomic and dermatological signs: conjunctival injection, rhinorrhea, excessive sweating, hypertension, and pruritic generalized rash, among others, immediately after carbidopa/levodopa administration regardless of the manufacturer. Treatment with dexamethasone combined with chloropyramine hydrochloride resulted in complete resolution of the hypersensitivity reaction each time it presented. The autonomic and dermatological manifestations did not reappear after treatment was replaced with benserazide/levodopa. CONCLUSIONS: To the best of our knowledge, this is the first case report of an allergic reaction specific to carbidopa. Our case highlights the importance of identifying the source of a hypersensitivity drug response, whether it is caused by the active component or by the excipients.

Autosomal dominant leukodystrophy presenting as Alzheimer's-type dementia.

Autosomal dominant leukodystrophy is a neurodegenerative disorder caused by either point mutations or duplication of the lamin B1 gene on chromosome 5q23. The typical clinical picture consists of autonomic symptoms as well as cerebellar and pyramidal signs. Here we present the case of a 57-year-old female referred to our clinic due to cognitive decline. Neurological examination was significant for cognitive impairment as well as pyramidal and cerebellar signs. Brain MRI displayed diffuse hyperintense lesions in the subcortical white matter, pontine nuclei, brachium pontis and restiform body. The diagnosis was confirmed via genetic testing. Autosomal dominant leukodystrophy should be included in the differential diagnosis of patients presenting with cognitive impairment, motor signs, and leukodystrophy-like images.

A Multicenter Comparative Study of Impulse Control Disorder in Latin American Patients With Parkinson Disease.

OBJECTIVES: Impulse control disorder (ICD) is a common adverse effect in patients with Parkinson disease who receive dopamine agonists; however, other factors are involved in its manifestations. To study the frequency and factors involved in the development of this adverse effect in a Latin American population, we conducted a cross-sectional multicenter study. METHODS: Two hundred fifty-five patients in 3 Latin American centers were evaluated by examination and application of scales (Unified Parkinson's Disease Rating Scale, Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale, Hoehn and Yahr, Clinical Impression of Severity Index for Parkinson's Disease). RESULTS: Of the patients, 27.4% had ICD, most of whom were on dopamine agonists. Other associated risk factors included a younger age at onset of Parkinson disease, moderate symptoms, a shorter evolution of the clinical manifestations, rapid eye movement (REM) sleep disorder behavior, and the consumption of tea, mate, and alcohol. CONCLUSIONS: The frequency of ICD is higher in Latin America than in Anglo-Saxon populations. Consuming tea and mate, in addition to the use of dopamine agonists, is a factor that may demonstrate a genetic link that predisposes patients to the establishment of an ICD.

Alcohol-Sensitive Generalized Dystonia.

We report the case of a 29-year-old male patient with a generalized and progressive dystonia that led him unable to stand. Multiple antidystonic treatments were tried without benefit. Alcohol test was positive with a dramatic improvement. To the best of our knowledge, this is the first reported case of generalized dystonia without other clinical manifestations sensitive to alcohol.

Successful Treatment of Brachial Plexopathy Due to Herpes Zoster Infection With Intravenous Immunoglobulin.

OBJECTIVE: The aim of this study was to report the case of a male patient with Parkinson disease who developed brachial plexopathy (BP) due to varicella-zoster virus, which was successfully treated with human immunoglobulin. METHOD: We report the case of a 75-year-old male subject with a diagnosis of Parkinson disease who came to our hospital complaining of pain, skin lesions, and strength loss in his right arm during the past 2 months. Physical examination revealed vesicular rash compatible with varicella-zoster virus lesions. Nerve conduction studies and magnetic resonance imaging of the brachial plexus showed inflammatory changes at that level. A trial with oral valacyclovir followed by intravenous methylprednisolone bolus was administered without further response. However, human intravenous immunoglobulin resulted in complete recovery of the symptoms. CONCLUSIONS: Human immunoglobulin is effective in BP due to zoster infection and must be considered if standard treatment fails. To the best of our knowledge, this is the first report of BP associated to zoster infection successfully treated with intravenous immunoglobulin.