Best Practices in the Clinical Management of Progressive Supranuclear Palsy and Corticobasal Syndrome: A Consensus Statement of the CurePSP Centers of Care.

Progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS; the most common phenotype of corticobasal degeneration) are tauopathies with a relentless course, usually starting in the mid-60s and leading to death after an average of 7 years. There is as yet no specific or disease-modifying treatment. Clinical deficits in PSP are numerous, involve the entire neuraxis, and present as several discrete phenotypes. They center on rigidity, bradykinesia, postural instability, gait freezing, supranuclear ocular motor impairment, dysarthria, dysphagia, incontinence, sleep disorders, frontal cognitive dysfunction, and a variety of behavioral changes. CBS presents with prominent and usually asymmetric dystonia, apraxia, myoclonus, pyramidal signs, and cortical sensory loss. The symptoms and deficits of PSP and CBS are amenable to a variety of treatment strategies but most physicians, including many neurologists, are reluctant to care for patients with these conditions because of unfamiliarity with their multiplicity of interacting symptoms and deficits. CurePSP, the organization devoted to support, research, and education for PSP and CBS, created its CurePSP Centers of Care network in North America in 2017 to improve patient access to clinical expertise and develop collaborations. The directors of the 25 centers have created this consensus document outlining best practices in the management of PSP and CBS. They formed a writing committee for each of 12 sub-topics. A 4-member Steering Committee collated and edited the contributions. The result was returned to the entire cohort of authors for further comments, which were considered for incorporation by the Steering Committee. The authors hope that this publication will serve as a convenient guide for all clinicians caring for patients with PSP and CBS and that it will improve care for patients with these devastating but manageable disorders.

Movement Disorder Emergencies.

Acute presentation of new movement disorders and acute decompensation of chronic movement disorders are uncommon but potentially life-threatening. Inadvertent or purposeful overdose of many psychiatric medications can result in acute life-threatening movement disorders including serotonin syndrome, neuroleptic malignant syndrome, and malignant catatonia. Early withdrawal of potentiating medications, treatment with benzodiazepines and other diagnosis-specific drugs, and providing appropriate supportive care including airway and breathing management, hemodynamic stabilization, fluid resuscitation, and renal support including possible hemodialysis are the mainstays of acute management. Many of these conditions require admission to the neurologic intensive care unit.

A Prospective Study of the Prevalence of Parkinsonism in Patients With Liver Cirrhosis.

Acquired hepatocerebral degeneration refers to a neurological syndrome consisting of various movement disorders and cognitive impairment in advanced liver cirrhosis or portosystemic shunt. Neurological signs and symptoms may be attributed to the accumulation of toxic substances in the brain. The most common neurological presentation of this is parkinsonism. Our prospective study aimed to investigate the prevalence of parkinsonism in patients with cirrhosis who were evaluated for liver transplant and to identify any correlation between findings on brain magnetic resonance imaging (MRI) and severity of parkinsonism. Of the 120 enrolled participants with liver cirrhosis, 62 (52%) exhibited signs of parkinsonism and all had MRI basal ganglia hyperintensity. Eighteen patients from this group were transplanted and showed statistically significant improvements in their Unified Parkinson's Disease Rating Scale (UPDRS) scores. Conclusion: The data suggest the reversibility of the neurological impairment seen in cirrhosis, and therefore the effectiveness of transplantation in improving parkinsonian symptoms. There was no correlation between severity of MRI findings and clinical motor UPDRS part III. Laboratory findings showed no correlation among the abnormal levels, MRI brain signal abnormality, or UPDRS scores.

CoQ10 in progressive supranuclear palsy: A randomized, placebo-controlled, double-blind trial.

OBJECTIVE: An investigator-initiated, multicenter, randomized, placebo-controlled, double-blind clinical trial to determine whether coenzyme Q10 (CoQ10) is safe, well tolerated, and effective in slowing functional decline in progressive supranuclear palsy (PSP). METHODS: Sixty-one participants received CoQ10 (2,400 mg/d) or placebo for up to 12 months. Progressive Supranuclear Palsy Rating Scale (PSPRS), Unified Parkinson's Disease Rating Scale, activities of daily living, Mini-Mental State Examination, the 39-item Parkinson's Disease Questionnaire, and 36-item Short Form Health Survey were monitored at baseline and months 3, 6, 9, and 12. The safety profile of CoQ10 was determined by adverse events, vital signs, and clinical laboratory values. Primary outcome measures were changes in PSPRS and Unified Parkinson's Disease Rating Scale scores from baseline to month 12. RESULTS: CoQ10 was well tolerated. No statistically significant differences were noted between CoQ10 and placebo groups in primary or secondary outcome measures. A nonsignificant difference toward slower clinical decline in the CoQ10 group was observed in total PSPRS among those participants who completed the trial. Before the final study visit at 12 months, 41% of participants withdrew because of travel distance, lack of perceived benefit, comorbidities, or caregiver issues. CONCLUSIONS: High doses of CoQ10 did not significantly improve PSP symptoms or disease progression. The high withdrawal rate emphasizes the difficulty of conducting clinical trials in patients with PSP. CLINICALTRIALSGOV IDENTIFIER: NCT00382824. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that CoQ10 does not significantly slow functional decline in PSP. The study lacks the precision to exclude a moderate benefit of CoQ10.

Spinal cord stroke: acute imaging and intervention.

Spinal cord infarction is an uncommon disease and as such is often a diagnostic challenge for clinicians. It can vary in its onset, severity, outcome, and recovery from patient to patient. Treatment options for this relatively rare condition also remain elusive. Current consensus recommendations are antiplatelet therapy and the symptomatic management of associated complications such as paraplegia and thromboembolic disease. There are multiple studies in surgical literature of a variety of interventions and adjuncts used for reducing the risk of ischemic spinal cord neurological injury, seen most often in the setting of thoracoabdominal aortic repair operations. We report two cases of acute non-surgical-related spinal cord infarcts, where early diagnosis was made and aggressive, early treatments instituted. With often devastating outcomes, we highlight the need for early detection and that interventions, commonly used in preventing neurological injury after high-risk aneurysm repairs, may be beneficial in treating and reducing the severity of disability in acute spinal cord stroke.

Transient parietal hand syndrome after cortical resection.

This case study with video recording describes a brief neurological examination of a rare post-surgical finding in a patient with intractable seizures who had a right parietal topectomy in order to cure focal and disabling epilepsy. Contemporaneously during the resection and while awake intraoperatively, the patient developed features characterised by involuntary, purposeless, and almost ballistic movements of the contralateral left upper extremity. These involved the shoulder and, more distally, the arm with less involvement of the hand itself and some clonic movement at the elbow, persisting for approximately 24 hours after surgery. Although identified in only one case in our series, we have named the resulting clinical phenomenology "parietal hand syndrome". A Medline search does not reveal any other such case in the English literature with the clinical elements and actual video documentation of neurological examination noted in our case report in the immediate post-operative setting. In this regard, this is a unique clinical report. [Published with video sequences].

Successful bilateral deep brain stimulation of the globus pallidus internus for persistent status dystonicus and generalized chorea.

The authors report the cases of 2 young male patients (aged 16 and 26 years) with dystonic cerebral palsy of unknown origin, who developed status dystonicus, an acute and persistent combination of generalized dystonia and chorea. Both patients developed status dystonicus after undergoing general anesthesia, and in 1 case, after administration of metoclopramide. In attempting to control this acute hyperkinetic movement disorder, multiple medication trials failed in both cases and patients required prolonged intubation and sedation with propofol. Bilateral deep brain stimulation of the globus pallidus internus (4 and 2 months after the onset of symptoms in the first and second case, respectively) produced immediate resolution of the hyperkinetic movement disorder in each case. Deep brain stimulation provided persistent suppression of the dystonic movement potential after a follow-up of 30 and 34 months, respectively, as demonstrated by the reemergence of severe dystonia during the end of battery life of the implantable pulse generators that was readily controlled by exchange of the generators in each case.

Motor cortex stimulation in patients with Parkinson disease: 12-month follow-up in 4 patients.

OBJECT: Since the initial 1991 report by Tsubokawa et al., stimulation of the M1 region of cortex has been used to treat chronic pain conditions and a variety of movement disorders. METHODS: A Medline search of the literature published between 1991 and the beginning of 2007 revealed 459 cases in which motor cortex stimulation (MCS) was used. Of these, 72 were related to a movement disorder. More recently, up to 16 patients specifically with Parkinson disease were treated with MCS, and a variety of results were reported. In this report the authors describe 4 patients who were treated with extradural MCS. RESULTS: Although there were benefits seen within the first 6 months in Unified Parkinson's Disease Rating Scale Part III scores (decreased by 60%), tremor was only modestly managed with MCS in this group, and most benefits seen initially were lost by the end of 12 months. CONCLUSIONS: Although there have been some positive findings using MCS for Parkinson disease, a larger study may be needed to better determine if it should be pursued as an alternative surgical treatment to DBS.

End of day dyskinesia in advanced Parkinson's disease can be eliminated by bilateral subthalamic nucleus or globus pallidus deep brain stimulation.

We report the therapeutic effects of deep brain stimulation (DBS) in 2 patients with Parkinson's disease (PD) with severe end of dose dyskinesia that was resistant to medical therapy. In both patients, severe, end of day ballistic dyskinesias occurred when the last levodopa dose of the day was wearing off. Globus pallidus (GPi) DBS in 1 case and subthalamic (STN) DBS in the second case produced full resolution of end of day dyskinesia.

Progression of Parkinson's disease following thalamic deep brain stimulation for tremor.

We assessed the long-term effect of thalamic deep brain stimulation (DBS) on motor symptoms and progression of Parkinson's disease (PD) in PD patients treated for resting and postural/action tremor. Thalamic DBS was performed in 17 patients with treatment-resistant resting and postural/action tremor. Nine patients were available for follow-up examination a mean of 5.5 years after surgery. Three had tremor-dominant PD. DBS produced marked improvement in resting and postural/action tremor in target upper extremity in all 9 patients, which persisted unchanged at the time of the last follow-up visit 5.5 years after surgery. PD severity with DBS 'on' and 'off' 1 year after surgery was compared to PD severity at the last follow-up visit using UPDRS (Unified Parkinson's Disease Rating Scale) III motor scores and individual motor item subscores. Patients were tested while on medication. There was no significant worsening of tremor, rigidity, speech, postural stability, gait, or axial bradykinesia with DBS either on or off at the last follow-up visit compared to the 12-month visit. UPDRS III motor scores were unchanged. However, global assessment of PD progression and increased mean L-dopa dose and L-dopa equivalent daily dose at the time of last follow-up visit indicated that a progression of PD had occurred.

Adverse effects of subthalamic nucleus DBS in a patient with multiple system atrophy.

A 59-year-old woman with levodopa-responsive parkinsonism complicated by motor fluctuations and generalized levodopa dyskinesia underwent bilateral subthalamic deep brain stimulation (STN DBS) 7 years after symptom onset. DBS improved levodopa-responsive upper extremity bradykinesia but aggravated speech, swallowing, and gait. Motor fluctuations were not improved and levodopa dose remained unchanged. Pulse generators were turned off. Clinical features and brain MRI in this case were indicative of multiple system atrophy (MSA). STN DBS is not recommended for patients with MSA.