Hand, foot, and spine deformities in parkinsonian disorders.

Hand and foot deformities, known as "striatal deformities", and other musculoskeletal abnormalities such as dropped head, bent spine, camptocormia, scoliosis and Pisa syndrome, are poorly understood and often misdiagnosed features of Parkinson's disease and other parkinsonian syndromes. These deformities share some similarities with known rheumatologic conditions and can be wrongly diagnosed as rheumatoid arthritis, osteoarthritis, psoriatic arthritis, Dupuytren's contracture, trigger finger, or other rheumatologic or orthopedic conditions. Neurologists, rheumatologists, and other physicians must be familiar with these deformities to prevent misdiagnosis and unnecessary diagnostic tests, and to recommend appropriate treatment options.

Restless Legs Syndrome: clinical features, diagnosis and a practical approach to management.

Restless legs syndrome (RLS) is a chronic neurological disorder that interferes with rest and sleep. It has a wide spectrum of symptom severity, and treatment is started when symptoms become bothersome. Dopamine agonists and calcium channel apha-2-delta antagonists (gabapentin, gabapentin enacarbil and pregabalin) are first-line treatments; calcium channel alpha-2-deltas are preferred over dopamine agonists because they give less augmentation, a condition with symptom onset earlier in the day and intensification of RLS symptoms. Dopamine agonists can still be used as first-line therapy, but the dose should be kept as low as possible. Iron supplements are started when the serum ferritin concentration is ≤75 µg/L, or if the transferrin saturation is less than 20%. For severe or resistant RLS, a combined treatment approach can be effective. Augmentation can be very challenging to treat and lacks evidenced-based guidelines.

Apraclonidine in the treatment of ptosis.

Transient ptosis is a known complication of botulinum toxin (BoNT) injection due to inadvertent migration of toxin into the levator palpebrae superioris muscle. Currently there is no treatment available for BoNT induced ptosis. Apraclonidine hydrochloride is a topical ophthalmic solution with selective alpha-2 and weak alpha-1 receptor agonist activity that has the ability to elevate the eye lid. Apraclonidine has been used as a diagnostic test in Horner's syndrome. We evaluated the effects apraclonidine in a cohort of BoNT induced ptosis and a patient with Horner syndrome. Each patient was administered 2 drops of apraclonidine 0.5% solution to the eye with the ptosis and was re-examined 20-30min later. All 6 patients showed improvement in ptosis. There was also improvement in ptosis in a patient with Horner's syndrome. Apraclonidine is not only useful as a diagnostic test in Horner's syndrome, but may be an effective and safe treatment for BoNT-induced ptosis.

Treatment of blepharospasm with apraclonidine.

OBJECTIVE: To describe improvement in blepharospasm with apraclonidine. BACKGROUND: Blepharospasm is a focal dystonia involving chiefly the orbicularis oculi and periocular muscles resulting in involuntary sustained eyelid closure. Botulinum toxin injection is the mainstay of treatment with meaningful improvement in over 85% of patients, but the effects often wear off within 3-4months. Apraclonidine is an alpha-2 adrenergic receptor agonist, which causes contraction of superior tarsal (Müller) muscle which may improve blepharospasm-related eyelid closure. We propose that apraclonidine may be a useful short-term treatment in patients with blepharospasm, particularly during wearing off from botulinum toxin injection. METHODS: Patients who had pre-mature wearing off of botulinum injection effect were evaluated before and after the administration of 2 drops of apraclonidine 0.5%-1% solution to each eye. Subjective patient impressions and examiner's impression of symptoms pre and post-apraclonidine administration were recorded. A blinded rater evaluated the videos and provided an independent assessment of the severity of symptoms pre- and post-administration, using a 0-4 scale. RESULTS: Our study included 7 patients (4 male) with a mean age of 61years and mean duration of blepharospasm of 3.6years. There was a subjective, albeit transient (about 2-4h) improvement in blepharospasm reported by all patients and by the examiner. The mean severity scores, based on blinded video ratings, showed a reduction from of 3.4 pre-administration to 2.3 post-administration of apraclonidine (p<0.025). No adverse effects were noted. CONCLUSIONS: Apraclonidine is a potentially useful medication for short term management of blepharospasm symptoms while awaiting botulinum toxin injection.

Movement Disorders From the Use of Metoclopramide and Other Antiemetics in the Treatment of Migraine.

Nausea and vomiting are a frequent accompaniment of migraine and anti-nausea medications are frequently used in its management. The majority of anti-nausea medications that are used in migraine are dopamine receptor blocking agents and therefore have the potential to cause drug-induced movement disorders. This article explores the risk of such drug-induced movement disorders in migraineurs who were treated with these medications.

Dopa-responsive dystonia--clinical and genetic heterogeneity.

Dopa-responsive dystonia (DRD) encompasses a group of clinically and genetically heterogeneous disorders that typically manifest as limb-onset, diurnally fluctuating dystonia and exhibit a robust and sustained response to levodopa treatment. Autosomal dominant GTP cyclohydrolase 1 deficiency, also known as Segawa disease, is the most common and best-characterized condition that manifests as DRD, but a similar presentation can be seen with genetic abnormalities that lead to deficiencies in tyrosine hydroxylase, sepiapterin reductase or other enzymes that are involved in the biosynthesis of dopamine. In rare cases, DRD can result from conditions that do not affect the biosynthesis of dopamine; single case reports have shown that DRD can be a manifestation of hereditary spastic paraplegia type 11, spinocerebellar ataxia type 3 and ataxia telangiectasia. This heterogeneity of conditions that underlie DRD frequently leads to misdiagnosis, which delays the appropriate treatment with levodopa. Correct diagnosis at an early stage requires use of the appropriate diagnostic tests, which include a levodopa trial, genetic testing (including whole-exome sequencing), cerebrospinal fluid neurotransmitter analysis, the phenylalanine loading test, and enzyme activity measurements. The selection of tests for use depends on the clinical presentation and level of complexity. This Review presents the common and rarer causes of DRD and their clinical features, and considers the most appropriate approaches to ensure early diagnosis and treatment.

Restless legs syndrome: clinical presentation diagnosis and treatment.

Restless legs syndrome (RLS) is a circadian disorder of sensory-motor integration that may be related to genetically determined dysregulation of iron transport across the blood-brain barrier. Dopamine agonists (DAs) have been considered the first-line therapy, but with the growing appreciation of problems associated with long-term treatment, particularly augmentation and impulse control disorder, alpha-2-delta drugs, such as gabapentin, are now considered the first line of treatment in patients with troublesome RLS. Opioids can be considered as an alternative therapy, particularly in patients with DA-related augmentation. In more severe cases, a combination therapy may be required. Intravenous iron therapy may be considered on those patients with refractory RLS.

SPG11 Mutations Associated With a Complex Phenotype Resembling Dopa-Responsive Dystonia.

BACKGROUND: The aim of this study was to describe a case of hereditary spastic paraplegia (HSP) resulting from SPG11 mutations, presenting with a complex phenotype of dopa-responsive dystonia (DRD), diagnosed using whole exome sequencing (WES). HSP resulting from SPG11 typically presents with spasticity, cognitive impairment, and radiological evidence of thin corpus callosum. Initial presentation with DRD has not been previously reported on. METHODS: This 11-year-old boy with delay in fine motor skills, presented at 8 years of age with progressive, generalized dystonia with diurnal variation, bradykinesia, and stiff gait. There was marked improvement in dystonia with levodopa, but he soon developed wearing-off phenomenon and l-dopa-induced dyskinesia. Family history was unremarkable. RESULTS: Brain MRI showed thinning of the anterior corpus callosum with periventricular white matter changes. 123I-ioflupane single-photon emission coupled tomography showed bilateral severe presynaptic dopamine deficiency. WES identified transheterozygous allelic variants in the SPG11 on chromosome 15, including a truncating STOP mutation (p.E1630X) and a second heterozygous coding variant (p.L2300R). Dystonia improved with globus pallidus internus (GPi) DBS surgery. CONCLUSIONS: HSP resulting from SPG11 should be considered in the differential diagnosis of a patient presenting with DRD, parkinsonism, and spasticity. This case expands the HSP genotype and phenotype. GPi DBS may be a therapeutic option in selected patients.

Movement disorders in catatonia.

Catatonia is a complex neuropsychiatric syndrome characterised by a broad range of motor, speech and behavioural abnormalities. 'Waxy flexibility', 'posturing' and 'catalepsy' are among the well-recognised motor abnormalities seen in catatonia. However, there are many other motor abnormalities associated with catatonia. Recognition of the full spectrum of the phenomenology is critical for an accurate diagnosis. Although controlled trials are lacking benzodiazepines are considered first-line therapy and N-Methyl-d-aspartate receptor antagonists also appears to be effective. Electroconvulsive therapy is used in those patients who are resistant to medical therapy. An underlying cause of the catatonia should be identified and treated to ensure early and complete resolution of symptoms.

Long-term efficacy and safety of fluphenazine in patients with Tourette syndrome.

OBJECTIVES: Haloperidol and pimozide are the only drugs currently approved by the U.S. Food and Drug Administration for treatment of Tourette syndrome (TS), but their potential side effects, which include tardive dyskinesia (TD), limit their use. METHODS: We performed a retrospective chart review of patients with TS treated with fluphenazine over a 26-year period. RESULTS: Among 268 patients with TS, fluphenazine was initiated at a mean age of 15.8 ± 10.7 years (range, 4.1-70.2) and titrated to an optimal dose of 3.24 ± 2.3 mg/day (range, 0.5-12.0), which was continued for an average of 2.6 ± 3.2 years (range, 0.01-16.8). Marked to moderate improvement was noted in 211 (80.5%). The most common side effects included drowsiness, fatigue, or both, observed in 70 (26.1%) patients. There were no cases of TD. CONCLUSIONS: Fluphenazine appears to be safe and effective in the treatment of TS, and there were no cases of TD in this cohort treated up to 16.8 years.

Short report: A calcified Taenia solium granuloma associated with recurrent perilesional edema causing refractory seizures: histopathological features.

We describe the first detailed histological description of an excised calcified Taenia solium granuloma from a patient who developed recurrent seizures associated with perilesional edema surrounding a calcified cysticercus (PEC). The capsule, around a degenerated cysticercus, contained marked mononuclear infiltrates that extended to adjacent brain, which showed marked astrocytosis, microgliosis, and inflammatory perivascular infiltrates. The presence of large numbers of mononuclear cells supports an inflammatory cause of PEC. Immunosuppression or anti-inflammatory measures may be able to treat and prevent PEC and recurrent seizures.

Hemidystonia-hemiatrophy syndrome.

UNLABELLED: To define the clinical and radiological features of patients with the combination of hemidystonia (HD) and hemiatrophy (HA), the HD-HA syndrome. HD is a very disabling neurological condition that is rarely associated with HA of the affected body part, similar to the hemiparkinsonism-hemiatrophy syndrome. METHOD: We reviewed the medical records of 26 patients with the HD-HA syndrome and the data was entered into a database and analyzed. Video recordings as well as imaging studies were also reviewed. Twenty six patients (14 female) with a mean age at onset of HD at 14.9 years (1-46 years) were followed for a mean of 3.4 years. Fourteen (53%) had HD and HA on the left side and 23 (88%) had hemiparesis preceding the onset of HD. The mean latency from the onset of hemiparesis to the onset of HD was 14.7 years (2 weeks-46 years). All patients with hemiparesis had marked improvement in their weakness prior to the onset of HD. Common causes leading to hemiparesis and subsequent HD were birth or perinatal complications (N = 13) and stroke (N = 10). Seven patients (26%) had associated seizures. Twenty two patients (85%) had abnormal brain MRI: eight had lesions directly involving the basal ganglia and nine had cerebral hemiatrophy or non specific diffuse atrophy. Sixteen patients received botulinum toxin injections and responded well to treatment. HD-HA is usually associated with static encephalopathy originating at very young age, but the syndrome may also represent delayed sequelae of a stroke or brain injury.

Hemiparkinsonism-hemiatrophy syndrome.

OBJECTIVE: To characterize the clinical and radiologic features of hemiparkinsonism-hemiatrophy syndrome (HPHA). METHODS: Medical records of patients with evidence of unilateral parkinsonism and ipsilateral body atrophy, evaluated at the Baylor College of Medicine Movement Disorders Clinic, were reviewed. RESULTS: The mean age at onset of the 30 patients who satisfied the criteria was 44.2 (15 to 63) years with a mean duration of symptoms for 9.7 (2 to 20) years. Half of all patients had dystonia at onset and dystonia was present in 21 (70%) patients during the course of the syndrome. Eleven (37%) also had scoliosis. Brain asymmetry on imaging studies was noted in 9 (30%) patients. Response to levodopa was rated as good in 18, moderate in 6, and poor in 6. Nine of 19 (47%) patients in whom birth history was available had difficult birth or had severe febrile illness in the first few months of life. Overall 10 (33%) patients had difficulty in walking during early childhood. CONCLUSION: Although the clinical features of hemiparkinsonism-hemiatrophy syndrome are variable, suggesting a heterogeneous pathogenesis, perinatal and early childhood cerebral injury appears to play an important role in about half of the cases.

Paroxysmal kinesigenic dyskinesia.

Paroxysmal kinesigenic dyskinesia (PKD) is a rare disorder characterised by brief and frequent attacks of abnormal involuntary movements induced by sudden movement. This disorder has not been reported previously in Sri Lanka. We studied six patients with respect to clinical presentation, aetiology, family history and response to treatment, and describe the Sri Lankan patterns of this illness. All the patients were males and the age at onset was from 11 to 22 years. The involuntary movements in all were dystonic and affected one or both sides, involving the face in the majority. All had difficulty in speaking during the attacks. One patient had an occasional attack during exercise. In all, the illness was sporadic, none had a family history of a similar illness and in none was it due to a secondary cause. The attacks usually lasted 10-60 seconds, and occurred up to 20 times a day. All patients responded well to anticonvulsants. PKD in Sri Lanka has a pattern similar to that described worldwide.