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Introduction: Spastic paraplegia type 4 (SPG4), resulting from heterozygous mutations in the SPAST gene, is the most common form among the heterogeneous group of hereditary spastic paraplegias (HSPs). We aimed to study genetic and clinical characteristics of SPG4 across Canada., Methods: The SPAST gene was analyzed in a total of 696 HSP patients from 431 families by either HSP-gene panel sequencing or whole exome sequencing (WES). We used Multiplex ligation-dependent probe amplification to analyze copy number variations (CNVs), and performed in silico structural analysis of selected mutations. Clinical characteristics of patients were assessed, and long-term follow-up was done to study genotype-phenotype correlations., Results: We identified 157 SPG4 patients from 65 families who carried 41 different SPAST mutations, six of which are novel and six are CNVs. We report novel aspects of mutations occurring in Arg499, a case with homozygous mutation, a family with probable compound heterozygous mutations, three patients with de novo mutations, three cases with pathogenic synonymous mutation, co-occurrence of SPG4 and clinically isolated syndrome, and novel or rarely reported signs and symptoms seen in SPG4 patients., Conclusion: Our study demonstrates that SPG4 is a heterogeneous type of HSP, with diverse genetic features and clinical manifestations. In rare cases, biallelic inheritance, de novo mutation, pathogenic synonymous mutations and CNVs should be considered., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: Parkinson's disease (PD) is neurodegenerative movement disorder affecting primarily the central nervous system with several recognized non-motor symptoms that can occur at various stages of the disease. Recently it has been shown that patients with PD may be prone to peripheral nervous system pathology in the form of a peripheral neuropathy (PN). It is unclear if PN is an inherent feature of PD or if it is an iatrogenic effect of the mainstay PD treatment Levodopa., Methods: To determine if peripheral neuropathy occurs in early untreated PD we employed a case-control study design using gold standard tests for PN, including neurological examination according to the Utah Early Neuropathy Scale (UENS) and nerve conduction studies, as well as new, more sensitive and informative tests for PN including the skin biopsy and corneal confocal microscopy (CCM)., Results: We studied 26 patients with PD and 22 controls using the neurological examination and nerve conduction studies (NCS) and found no significant difference between groups except for some reduced vibration sense in the PD group. Epidermal nerve densities in the skin biopsies were similar between our cohorts. However, using CCM - a more sensitive test and a surrogate marker of small fiber damage in PN, we found that patients with PD had significantly reduced corneal nerve fiber densities and lengths as compared to controls., Conclusions: We conclude that our positive CCM results provide evidence of preclinical PN in newly diagnosed PD patients., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objectives: To explore current practices and opinions regarding hospital management of Parkinson disease (PD) patients in specialized PD Centers., Methods: Fifty-one out of 54 National Parkinson Foundation (NPF) Centers worldwide completed an online survey regarding hospitalization of PD patients., Results: Many Centers were concerned about the quality of PD-specific care provided to their patients when hospitalized. Primary concerns were adherence to the outpatient medication schedule and poor understanding by hospital staff of medications that worsen PD. Few Centers had a policy with their primary hospital that notified them when their patients were admitted. Rather, notification of hospitalization came often from the patient or a family member. Several Centers (29%) reported not finding out about a hospitalization until a routine clinic visit after discharge. Quick access to outpatient PD care following discharge was a problem in many Centers. Elective surgery, fall/fracture, infection, and mental status changes, were identified as common reasons for hospitalization., Conclusions: There is a perceived need for PD specialists to be involved during hospitalization of their patients. Improvement in communication between hospitals and PD Centers is necessary so that hospital clinicians can take advantage of PD specialists' expertise. Education of hospital staff and clinicians regarding management of PD, complications of PD, and medications to avoid in PD is critical. Most importantly, outpatient access to PD specialists needs to be improved, which may prevent unnecessary hospitalizations in these patients., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Objective: To review the literature and to identify practice gaps in the management of the hospitalized Parkinson's disease (PD) patient., Background: Patients with PD are admitted to hospitals at higher rates, and frequently have longer hospital stays than the general population. Little is known about outpatient interventions that might reduce the need for hospitalization and also reduce hospital-related complications., Methods: A literature review was performed on PubMed about hospitalization and PD between 1970 and 2010. In addition, in press peer-reviewed papers or published abstracts known to the authors were included. Information was reviewed by a National Parkinson Foundation workgroup and a narrative review article was generated., Results: Motor disturbances in PD are believed to be a causal factor in the higher rates of admissions and complications. However, other conditions are commonly recorded as the primary reason for hospitalization including motor complications, reduced mobility, lack of compliance, inappropriate use of neuroleptics, falls, fractures, pneumonia, and other important medical problems. There are many relevant issues related to hospitalization in PD. Medications, dosages and specific dosage schedules are critical. Staff training regarding medications and medication management may help to avoid complications, particularly those related to reduced mobility, and aspiration pneumonia. Treatment of infections and a return to early mobility is also critical to management., Conclusions: Educational programs, recommendations, and guidelines are needed to better train interdisciplinary teams in the management of the PD patient. These initiatives have the potential for both cost savings and improved outcomes from a preventative and a hospital management standpoint., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Dopamine agonists (DA) have been associated with pathological gambling (PG) and other compulsive behaviors in Parkinson's disease (PD). Although these medications are used in other conditions, we are not aware of other reports of PG exclusive to treatment for idiopathic PD. We present a case of PG arising in the context of DA use for restless legs syndrome.

The Unified Parkinson's Disease Rating Scale (UPDRS) activities of daily living (ADL) items have been described as reflecting both disability (true ADL items) and impairment (rather than ADLs). As a result of combining these scores, UPDRS part II scores may not accurately reflect the impact of surgery on ADLs [Hariz G.M., Lindberg M., Hariz M.I., Bergenheim A.T. Does the ADL part of the unified Parkinson's disease rating scale measure ADL? An evaluation in patients after pallidotomy and thalamic deep brain stimulation. Mov Disord 2003;18:373-81.]. The goal of the present study was to assess the metric properties of the ADL section of the UPDRS in terms of its ability to measure surgical change. We tested the effects of unilateral pallidotomy (N=14) and bilateral subthalamic nucleus (STN) DBS (N=11) on both disability and impairment components of the UPDRS-II at uniform follow-up assessment periods of 6 months and 1 year, with a subset of pallidotomy patients (N=9) re-assessed at 2 years. Across the follow-up periods in both patient groups, items identified as best reflecting disability showed significant improvement from pre-surgical levels, whereas items representing impairment showed no overall change. Consistent with this, change in total ADL scores was tempered by the inclusion of the impairment items. Because the measurement of a patient's functional status is important in determining the effectiveness of an intervention, analysis of appropriate items from the UPDRS ADL section is imperative.

This study investigated the effect of Parkinson's disease (PD) on the time course for postural control following the removal and reinsertion of visual information. Twelve medicated PD patients (PD) and 12 age matched control (CTRL) subjects performed two 45-s quiet standing trials, during which visual feedback was available (0-15s), deprived (15-30s), and then restored (30-45s). The 45s test trial was divided into 5s time bins to compare the time-based effect of sensory reorganization during deprivation and reintegration. Results revealed an increase in Elliptical Sway Area (ESA) following visual deprivation for both groups; this increased ESA remained significantly higher than the baseline level for the duration of the deprivation period among PD patients and returned to baseline the level among CTRL. Despite elevated ESA at the end of visual deprivation among PD patients, neither group showed a change in ESA after visual information was restored. These results indicate a PD-associated deficit with the reorganization of sensory priorities for postural control, and may implicate the basal ganglia as being critical for integration of sensory information for postural control.

Inherited ataxias are a heterogeneous group of disorders characterized by autosomal dominant and recessive inheritance. Recent advances in genetic research have resulted in an improved comprehension of their clinical presentation. Autosomal dominant cerebellar ataxias (ADCAs) include spinocerebellar ataxias (SCAs) and dentatorubral-pallidoluysian atrophy (DRPLA); six of these have been found to be trinucleotide repeat disorders. Episodic ataxia, types 1 and 2, are at present recognized to be channelopathies, caused by point mutations. Friedreich's ataxia (FA) which is an autosomal recessive disorder, resulting from a a unique trinucleotide repeat, is now recognized to have a wide age of onset and clinical spectrum. Ataxia-telangiectasia (AT), also an autosomal recessive cerebellar ataxia, is characterized by immunodeficiency. In this article, the genetic and clinical characteristics of these diseases are reviewed in detail.