Top-Up Clozapine for Risperidone LAI-Related Acute Dystonia and TR Bipolar in an Adolescent with ID-Putting the Cart before the Horse?

Objectives: Young patients with intellectual disability (ID) have both diagnostic and therapeutic challenges. These include, inter alia, diagnostic overshadowing, diagnostic slippage and heightened vulnerability to adverse drug reactions. These would portent a generally poor prognostication. Methods: This is a case-study of an adolescent with intellectual disability long-hospitalized for co-morbid treatment-resistant bipolar mood disorder that failed to respond to ECT. Patient partially responded to LAI risperidone with repeated ADRs. Top-up with low-dose clozapine (100 mg/d) was pursued. Results: Low-dose clozapine top-up complemented therapeutic response (mood lability and paranoia) and strikingly safeguarded effectively against risperidone-related extrapyramidal side effects. Conclusions: Add-on clozapine remains a viable option, albeit off-label, in young patients with ID and treatment-resistant affective/schizophreniform psychoses. Clozapine has an edge over other agents in the setting of dyskinesias.

[Focal or Segmental Dystonia Resistant to Botulinum Toxin: How Do You Treat Patients in Whom Botulinum Toxin Treatment Has No Effect?]

Botulinum toxin treatment is most commonly used for blepharospasm, spastic torticollis, upper limb dystonia, and local dystonia in Japan. Botulinum toxin treatment is the first choice in these conditions. However, it has the disadvantages that the therapeutic effect is transient, that there are cases in whom the treatment is ineffective, and a high cost. In ineffective cases, botulinum toxin treatment involves medication and rehabilitation. Various medications have been used for the treatment of focal dystonia mainly in open trials. As these treatments have low evidence levels, each case should be dealt with individually. Operative treatment should be considered for severe cases.

Striatal Synaptic Dysfunction in Dystonia and Levodopa-Induced Dyskinesia.

This review provides an overview of the synaptic dysfunctions of neuronal circuits and underlying neurochemical alterations observed in the hyperkinetic movement disorders, dystonia and dyskinesia. These disorders exhibit similar changes in expression of synaptic plasticity and neuromodulation. This includes alterations in physical attributes of synapses, synaptic protein expression, and neurotransmitter systems, such as glutamate and gamma-aminobutyric acid (GABA), and neuromodulators, such as dopamine, acetylcholine, serotonin, adenosine, and endocannabinoids. A full understanding of the mechanisms and consequences of disruptions in synaptic function and plasticity will lend insight into the development of these disorders and new ways to combat maladaptive changes.

Frequency and risk factors of antibody-induced secondary failure of botulinum neurotoxin therapy.

OBJECTIVE: To investigate the risk factors of neutralizing antibody (NAB)-induced complete secondary treatment failure (cSTF) during long-term botulinum neurotoxin (BoNT) treatment in various neurologic indications. METHODS: This monocenter retrospective cohort study analyzed the data of 471 patients started on BoNT therapy between 1995 and 2015. Blood samples of 173 patients were investigated for NABs using the mouse hemidiaphragm test (93 with suspected therapy failure, 80 prospective study participants). The frequency of NAB-cSTF was assessed for various indications: hemifacial spasm, blepharospasm, cervical dystonia, other dystonia, and spasticity. A priori defined potential risk factors for NAB-cSTF were evaluated, and a stepwise binary logistic regression analysis was performed to identify independent risk factors. RESULTS: Treatment duration was 9.8 ± 6.2 years (range, 0.5-30 years; adherence, 70.6%) and number of treatment cycles 31.2 ± 22.5 (3-112). Twenty-eight of 471 patients (5.9%) had NAB-cSTF at earliest after 3 and at latest after 103 treatment cycles. None of the 49 patients treated exclusively with incobotulinumtoxinA over 8.4 ± 4.2 (1-14) years developed NAB-cSTF. Independent risk factors for NAB-cSTF were high BoNT dose per treatment, switching between onabotulinumtoxinA and other BoNT formulations (except for switching to incobotulinumtoxinA), and treatment of neck muscles. CONCLUSIONS: We present a follow-up study with the longest duration to date on the incidence of NAB-cSTF in patients treated with various BoNT formulations, including incobotulinumtoxinA. Whereas the overall risk of NAB-cSTF is low across indications and BoNT formulations, our findings underpin the recommendations to use the lowest possible dose particularly in cervical dystonia, and to avoid unnecessary switching between different formulations.

Acute cerebellar knockdown of Sgce reproduces salient features of myoclonus-dystonia (DYT11) in mice.

Myoclonus dystonia (DYT11) is a movement disorder caused by loss-of-function mutations in SGCE and characterized by involuntary jerking and dystonia that frequently improve after drinking alcohol. Existing transgenic mouse models of DYT11 exhibit only mild motor symptoms, possibly due to rodent-specific developmental compensation mechanisms, which have limited the study of neural mechanisms underlying DYT11. To circumvent potential compensation, we used short hairpin RNA (shRNA) to acutely knock down Sgce in the adult mouse and found that this approach produced dystonia and repetitive, myoclonic-like, jerking movements in mice that improved after administration of ethanol. Acute knockdown of Sgce in the cerebellum, but not the basal ganglia, produced motor symptoms, likely due to aberrant cerebellar activity. The acute knockdown model described here reproduces the salient features of DYT11 and provides a platform to study the mechanisms underlying symptoms of the disorder, and to explore potential therapeutic options.

Acute onset of orofacial dystonia from promethazine treatment: A case report.

RATIONALE: Promethazine is an antihistamine agent used commonly for nausea and allergy. Along with its anticholinergic and antidopaminergic functions, promethazine is also used for psychiatric symptoms, such as troubling sleep, anxiety, and agitation. Previous studies have reported that promethazine may occasionally elicit acute dystonia in some individuals, especially for young children and pregnant women. PATIENT CONCERNS: The 68-year-old female patient was admitted to our hospital because of feeling anxious and intermittent palpitation for over 1 year. She developed acute orofacial dystonia following promethazine treatment. DIAGNOSES: Her diagnoses was generalized anxiety disorder. INTERVENTIONS: Discontinuation of the offending agent, promethazine, and injection of Botulinum toxin. OUTCOMES: The acute orofacial dystonia was finally alleviated by local injection of Botulinum toxin. LESSONS: Careful assessment of the risk of developing acute dystonia is also needed in old patients when initiating the promethazine treatment.

Setting the record straight: The nosology of tardive syndromes.

We propose the use of the term tardive dyskinesia to refer to the original description of repetitive and complex oral-buccal-lingual (OBL) movements and the analogous repetitive movements of the limbs, trunk, or pelvis. The term tardive syndrome is an umbrella term to be used to refer to the spectrum of all persistent hyperkinetic, hypokinetic, and sensory phenomenologies resulting from chronic dopamine receptor blocking agent (DRBA) exposure. TD is a type of TS. The term tardive dystonia (TDyst) should be used when dystonia is the main feature of TS. Retrocollis and oromandibular dystonia appear to be the most common form of Tdyst. Tardive akathisia refers to the inability to remain still with an urge to move, giving the appearance of restlessness. In tardive tourettism, the patient has complex motor and phonic tics associated with premonitory urge and relief of tension after performing the tic behavior, thus resembling Tourette's syndrome. Tardive tremor is composed of mainly postural and kinetic tremors. It differs from the resting tremor seen in drug-induced parkinsonism. Tardive pain occurs in association with chronic use of DRBAs and involves the mouth, tongue, and genital region with no physical findings. In tardive parkinsonism, the patient has persistent parkinsonism even after discontinuation of the DRBA although this diagnosis is in question and may represent DRBA-uncovered idiopathic Parkinson's disease or coincident development of Parkinson's disease while taking DRBAs.

Acute Focal Dystonia After a Single Dose of Oral Cetirizine in a 9-Year-Old Boy.

Common cold is an acute illness affecting pediatric population in particular. The use of antihistamines is a common practice, with cetirizine being a frequently used drug with a good safety profile. However, adverse events due to the use of antihistamines have been rarely reported, such as drug-induced dystonia with the use of cetirizine. In our present case, dystonia due to the intake of cetirizine was observed, which the patient responded well to the use of benzodiazapines, namely, clonazepam. We report this case to highlight the occurrence of this adverse event with the use of cetirizine.

[Pisa syndrome associated with codeine]. / Sindrome de Pisa asociado a codeina.

TITLE: Sindrome de Pisa asociado a codeina.

Oculogyric Crises.

BACKGROUND: Oculogyric crises are involuntary movements of the eyeballs and can occur due to different etiologies. PHENOMENOLOGY SHOWN: This video abstract shows a man with oculogyric crises due to side effect of neuroleptics. EDUCATIONAL VALUE: Oculogyric crises are easy to recognize if once seen.

Pisa syndrome due to donepezil: pharmacokinetic interactions to blame?

We report a case of Pisa syndrome (PS) due to the acetylcholinesterase inhibitor donepezil which may have been precipitated by pharmacokinetic interactions with commonly used medications. PS is defined as a reversible lateral bending of the trunk with a tendency to lean to one side. This is a rare but very distressing complication with this commonly used medication which was not initially recognised, leading to increasing disability for the patient and significant carer stress. Cessation of donepezil and modulation of potential interacting medications resulted in complete resolution.

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.

Recurrent and Alternating Pisa Syndrome.

OBJECTIVES: The aims of the study were to report the case of a male patient who developed a first episode of Pisa syndrome (PS) to the right side and a second episode to the left side and to discuss the hypothesis that states that denervation is one of the main mechanisms implicated in the development of PS. METHODS: We report on the case of a 71-year-old patient with Parkinson disease who developed PS to the right side while on dopaminergic treatment with pramipexol and levodopa. The dopamine agonist was discontinued and the postural abnormality was corrected increasing the levodopa dose. Six years later, while on ropinirole and levodopa, he developed PS again but this time the lean was to the left. Even though the dopamine agonist was discontinued, this condition failed to improve. CONCLUSIONS: Mechanisms other than denervation and its relationship with the more or less affected side contribute to the development of the syndrome.This is the first report of a case of recurrent alternating PS and highlights the need for research on this topic to better understand this disorder.