DNAJC13 p.Asn855Ser mutation screening in Parkinson's disease and pathologically confirmed Lewy body disease patients.

BACKGROUND: Recently, a novel mutation in exon 24 of DNAJC13 gene (p.Asn855Ser, rs387907571) has been reported to cause autosomal dominant Parkinson's disease (PD) in a multi-incident Mennonite family. METHODS: In the present study the mutation containing exon of the DNAJC13 gene has been sequenced in a Caucasian series consisting of 1938 patients with clinical PD and 838 with pathologically diagnosed Lewy body disease (LBD). RESULTS: Our sequence analysis did not identify any coding variants in exon 24 of DNAJC13. Two previously described variants in intron 23 (rs200204728 and rs2369796) were observed. CONCLUSION: Our results indicate that the region surrounding the DNAJC13 p.Asn855Ser substitution is highly conserved and mutations in this exon are not a common cause of PD or LBD among Caucasian populations.

A retrospective study of the clinical and electrophysiological characteristics of 32 patients with orthostatic myoclonus.

OBJECTIVES: To review the electrophysiological and clinical characteristics of 32 patients with orthostatic myoclonus (OM), a relatively newly identified movement disorder, and compare these characteristics to those of primary orthostatic tremor (OT) patients and patients with similar gait and balance complaints without either hyperkinesia diagnosed during the same 30-month period. METHODS: The database of the Mayo Clinic Florida Movement Disorders Electrophysiology Laboratory (MDEL) was searched for all patients referred for possible OM or OT from 6/2010 to 12/2012. All available clinical records and archived surface electromyographical data for these patients were reviewed and analyzed. RESULTS: 32 patients with OM (mean age 74 years), 8 with primary OT (mean age 71), and 55 with neither orthostatic hyperkinesia (NOH) (mean age 68) were identified. All OT patients and 84% each of OM and NOH patients complained of involuntary leg movements while standing, e.g., "shaking," "trembling," or "jerking." All OM and OT patients experienced symptomatic and electrophysiological abatement or attenuation of their leg hyperkinesias by leaning forward onto an object while standing. CONCLUSIONS: OM has some similarities to OT, including causing "shaky legs" subjectively in standing older patients. Novel data from this work include that, as in OT, OM essentially abates when patients remove their weight from their legs. This shared isometric phenomenon may reflect that OT and OM are on a pathophysiological continuum. Further, many patients who complain of their legs "shaking" while standing may have neither OT nor OM. Surface electromyography may be a useful adjunct in extrapolating patients complaining of "shaky legs."

Office assessment of gait and station.

Gait and station disorders are among the most common reasons patients seek outpatient neurologic consultation. A careful assessment of gait and station provides the clinician with an overview of the integrity of a patient's central and peripheral nervous systems. Therefore, clinicians may consider performing a gait and station examination as the prelude to their formal neurologic examination of the patient, regardless of their chief complaint, to gain insight into which areas of the remainder of the neurologic examination they should particularly focus on, to localize the patient's neurologic dysfunction. In this review, the author describes how a structured gait and station examination may be performed in the ambulatory setting, without any special equipment. Then, the precise mechanics of each component of normal gait and station are discussed, so that the potential localizations and significance of abnormalities, which may occur during various phases of the gait cycle, can be highlighted. In particular, some less common findings are emphasized, which may be mistaken as psychogenic in etiology.

Novel THAP1 sequence variants in primary dystonia.

BACKGROUND: THAP1 encodes a transcription factor (THAP1) that harbors an atypical zinc finger domain and regulates cell proliferation. An exon 2 insertion/deletion frameshift mutation in THAP1 is responsible for DYT6 dystonia in Amish-Mennonites. Subsequent screening efforts in familial, mainly early-onset, primary dystonia identified additional THAP1 sequence variants in non-Amish subjects. OBJECTIVE: To examine a large cohort of subjects with mainly adult-onset primary dystonia for sequence variants in THAP1. METHODS: With high-resolution melting, all 3 THAP1 exons were screened for sequence variants in 1,114 subjects with mainly adult-onset primary dystonia, 96 with unclassified dystonia, and 600 controls (400 neurologically normal and 200 with Parkinson disease). In addition, all 3 THAP1 exons were sequenced in 200 subjects with dystonia and 200 neurologically normal controls. RESULTS: Nine unique melting curves were found in 19 subjects from 16 families with primary dystonia and 1 control. Age at dystonia onset ranged from 8 to 69 years (mean 48 years). Sequencing identified 6 novel missense mutations in conserved regions of THAP1 (G9C [cervical, masticatory, arm], D17G [cervical], F132S [laryngeal], I149T [cervical and generalized], A166T [laryngeal], and Q187K [cervical]). One subject with blepharospasm and another with laryngeal dystonia harbored a c.-42C>T variant. A c.57C>T silent variant was found in 1 subject with segmental craniocervical dystonia. An intron 1 variant (c.71+9C>A) was present in 7 subjects with dystonia (7/1,210) but only 1 control (1/600). CONCLUSIONS: A heterogeneous collection of THAP1 sequence variants is associated with varied anatomical distributions and onset ages of both familial and sporadic primary dystonia.

Leukoencephalopathy with spheroids (HDLS) and pigmentary leukodystrophy (POLD): a single entity?

Hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) and familial pigmentary orthochromatic leukodystrophy (POLD) present as adult-onset dementia with motor impairment and epilepsy. They are regarded as distinct diseases. We review data from the literature that support their being a single entity. Apart from a slightly older age at onset, a more rapid course, and more prominent pyramidal tract involvement, familial POLD is clinically similar to HDLS. Moreover, the pathologic hallmarks of the two diseases, axonal spheroids in HDLS and pigmented macrophages in POLD, can be identified in both conditions. This supports HDLS and POLD being referred collectively as adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP).

Insights into the dynamics of hereditary diffuse leukoencephalopathy with axonal spheroids.

OBJECTIVE: To report a new American family with hereditary diffuse leukoencephalopathy with spheroids (HDLS), including serial, presymptomatic and symptomatic, cranial MRIs from the proband. METHODS: We report clinical and genealogic investigations of an HDLS family, sequential brain MRIs of the proband, and autopsy slides of brain tissue from the proband's father. RESULTS: We identified seven affected family members (five deceased). The mean age at symptomatic disease onset was 35 years (range: 20-57), and the mean disease duration was 16 years (range: 3-46). Five affected individuals initially manifested memory disturbance and behavioral changes, whereas two experienced a mood disorder as their presenting symptom. Our proband's father had been diagnosed clinically with vascular dementia, but his brain autopsy was consistent with HDLS. The proband had a cranial MRI prior to symptom onset, with two subsequent MRIs performed during follow-up. These serial images reveal a progressive, confluent, frontal-predominant leukoencephalopathy with symmetric cortical atrophy. CONCLUSIONS: The proband of our newly identified hereditary diffuse leukoencephalopathy with spheroids (HDLS) kindred had subtle evidence of an incipient leukoencephalopathy on a presymptomatic cranial MRI. Conceivably, MRI may facilitate identifying affected presymptomatic individuals within known HDLS kindreds, increasing the likelihood of isolating the causative genes.

Progressive supranuclear palsy phenotype secondary to CADASIL.

BACKGROUND AND PURPOSE: To report a unique case of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy manifesting as a progressive supranuclear palsy phenotype, thereby expanding its recognized presentations. METHODS: Review of the pertinent literature from MEDLINE, cross-referencing cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, progressive supranuclear palsy, and parkinsonism. Description of a 60-year-old woman who presented with a several year history of step-wise, progressive parkinsonism secondary to cerebral autosomal dominant arteriopathy. RESULTS: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy may present with a progressive supranuclear phenotype. CONCLUSION: Parkinsonism, including a progressive supranuclear palsy phenotype, is one of a growing number of recognized ways that cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy may present.

Adult onset Niemann-Pick disease type C presenting with psychosis.

Niemann-Pick disease type C (NPC) is an autosomal recessive neurometabolic disorder that rarely presents in adulthood, and is associated with cognitive decline, various movement disorders (ataxia, chorea, dystonia, and myoclonus), a vertical supranuclear gaze palsy (VSGP), and seizures. A recent case report demonstrated a delay in diagnosis of eight years when a patient with NPC presented with psychosis. This article reviewed all cases seen at the Mayo Clinic with a possible diagnosis of NPC between 1976 and 2000. Of the 52 possible cases, five had an established diagnosis of adult onset NPC. Of these, two presented with psychosis and were not diagnosed with NPC for 5 and 15 years, respectively. NPC may initially present in adulthood with psychosis, and when psychosis is associated with VSGP, various dyskinesias, and seizures, NPC should be suspected.

Neurologic sequelae of west nile virus infection.

This review encompasses the extant literature on West Nile virus (WNV)-associated neurologic complications and also includes some of the author's experiences with Louisiana patients infected with WNV in the Summer of 2002 who sustained neurologic sequelae. In the appropriate clinical context, patients should be screened for WNV.

Drug-induced parkinsonism.

BACKGROUND: Drug-induced parkinsonism is common but often unrecognized. In addition to neuroleptics, many medications of diverse chemical nature may induce or exacerbate parkinsonism REVIEW SUMMARY: Reports in the literature of drug-induced parkinsonism or of an underlying parkinsonian disorder exacerbated by a medication were located using MEDLINE, and pertinent bibliographies were reviewed. The range of medications that may induce or exacerbate parkinsonism spans the medical specialties. Along with neuroleptics, selective-serotonin reuptake inhibitors, lithium, valproic acid, calcium channel blockers, antiarrhythmics, procholinergics, chemotherapeutics, amphotericin B, estrogens, and others have been implicated. CONCLUSIONS: This review seeks to enhance clinicians' knowledge of potential medications producing iatrogenic parkinsonism and encourage their vigilance in recognizing it.

Utility of an EMG mapping study in treating cervical dystonia.

Intramuscular injections of botulinum toxin are the cornerstone of treatment for cervical dystonia. Controversy exists regarding the necessity for EMG-guided injections. We compared the clinical examination of four movement disorder specialists to an electromyographic (EMG) mapping study. Clinical predictions of individual muscle involvement were only 59% sensitive and 75% specific. Muscle hypertrophy, shoulder elevation, and dominant head vector did not bolster clinical accuracy. An EMG mapping study facilitates identification of dystonic muscles in cervical dystonia, which may enhance botulinum toxin therapy.