Tim J. Anderson

The MoCA Well-suited screen for cognitive impairment in Parkinson disease

Objective: To establish the diagnostic accuracy of the Montreal Cognitive Assessment (MoCA) when screening externally validated cognition in Parkinson disease (PD), by comparison with a PD-focused test (Scales for Outcomes in Parkinson disease–Cognition [SCOPA-COG]) and the standardized Mini-Mental State Examination (S-MMSE) as benchmarks. Methods: A convenience sample of 114 patients with idiopathic PD and 47 healthy controls was examined in a movement disorders center. The 21 patients with dementia (PD-D) were diagnosed using Movement Disorders Society criteria, externally validated by detailed independent functional and neuropsychological tests. The 21 patients with mild cognitive impairment (PD-MCI) scored 1.5 SD or more below normative data in at least 2 measures in 1 of 4 cognitive domains. Other patients had normal cognition (PD-N). Results: Primary outcomes using receiver operating characteristic (ROC) curve analyses showed that all 3 mental status tests produced excellent discrimination of PD-D from patients without dementia (area under the curve [AUC], 87%–91%) and PD-MCI from PD-N patients (AUC, 78%–90%), but the MoCA was generally better suited across both assessments. The optimal MoCA screening cutoffs were <21/30 for PD-D (sensitivity 81%; specificity 95%; negative predictive value [NPV] 92%) and <26/30 for PD-MCI (sensitivity 90%; specificity 75%; NPV 95%). Further support that the MoCA is at least equivalent to the SCOPA-COG, and superior to the S-MMSE, came from the simultaneous classification of the 3 PD patient groups (volumes under a 3-dimensional ROC surface, chance = 17%: MoCA 79%, confidence interval [CI] 70%–89%; SCOPA-COG 74%, CI 62%–86%; MMSE-Sevens item 56%, CI 44%–68%; MMSE-World item 62%, CI 50%–73%). Conclusions: The MoCA is a suitably accurate, brief test when screening all levels of cognition in PD.

Rotigotine Effects on Early Morning Motor Function and Sleep in Parkinson's Disease: A Double-Blind, Randomized, pLacebo-Controlled Study (RECOVER)

In a multinational, double‐blind, placebo‐controlled trial (NCT00474058), 287 subjects with Parkinsons disease (PD) and unsatisfactory early‐morning motor symptom control were randomized 2:1 to receive rotigotine (2–16 mg/24 hr [n = 190]) or placebo (n = 97). Treatment was titrated to optimal dose over 1–8 weeks with subsequent dose maintenance for 4 weeks. Early‐morning motor function and nocturnal sleep disturbance were assessed as coprimary efficacy endpoints using the Unified Parkinsons Disease Rating Scale (UPDRS) Part III (Motor Examination) measured in the early morning prior to any medication intake and the modified Parkinsons Disease Sleep Scale (PDSS‐2) (mean change from baseline to end of maintenance [EOM], last observation carried forward). At EOM, mean UPDRS Part III score had decreased by −7.0 points with rotigotine (from a baseline of 29.6 [standard deviation (SD) 12.3] and by −3.9 points with placebo (baseline 32.0 [13.3]). Mean PDSS‐2 total score had decreased by −5.9 points with rotigotine (from a baseline of 19.3 [SD 9.3]) and by −1.9 points with placebo (baseline 20.5 [10.4]). This represented a significantly greater improvement with rotigotine compared with placebo on both the UPDRS Part III (treatment difference: −3.55 [95% confidence interval (CI) −5.37, −1.73]; P = 0.0002) and PDSS‐2 (treatment difference: −4.26 [95% CI −6.08, −2.45]; P < 0.0001). The most frequently reported adverse events were nausea (placebo, 9%; rotigotine, 21%), application site reactions (placebo, 4%; rotigotine, 15%), and dizziness (placebo, 6%; rotigotine 10%). Twenty‐four‐hour transdermal delivery of rotigotine to PD patients with early‐morning motor dysfunction resulted in significant benefits in control of both motor function and nocturnal sleep disturbances.

Impaired eye movements in post-concussion syndrome indicate suboptimal brain function beyond the influence of depression, malingering or intellectual ability

Post-concussion syndrome (PCS) can affect up to 20%-30% of patients with mild closed head injury (mCHI), comprising incomplete recovery and debilitating persistence of post-concussional symptoms. Eye movements relate closely to the functional integrity of the injured brain and eye movement function is impaired post-acutely in mCHI. Here, we examined whether PCS patients continue to show disparities in eye movement function at 3-5 months following mCHI compared with patients with good recovery. We hypothesized that eye movements might provide sensitive and objective functional markers of ongoing cerebral impairment in PCS. We compared 36 PCS participants (adapted World Health Organization guidelines) and 36 individually matched controls (i.e. mCHI patients of similar injury severity but good recovery) on reflexive, anti- and self-paced saccades, memory-guided sequences and smooth pursuit. All completed neuropsychological testing and health status questionnaires. Mean time post-injury was 140 days in the PCS group and 163 days in the control group. The PCS group performed worse on anti-saccades, self-paced saccades, memory-guided sequences and smooth pursuit, suggesting problems in response inhibition, short-term spatial memory, motor-sequence programming, visuospatial processing and visual attention. This poorer oculomotor performance included several measures beyond conscious control, indicating that subcortical functionality in the PCS group was poorer than expected after mCHI. The PCS group had poorer neuropsychological function (memory, complex attention and executive function). Analysis of covariance showed oculomotor differences to be practically unaffected by group disparities in depression and estimated intellectual ability. Compared with neuropsychological tests, eye movements were more likely to be markedly impaired in PCS cases with high symptom load. Poorer eye movement function, and particularly poorer subcortical oculomotor function, correlated more with post-concussive symptom load and problems on activities of daily living whilst poorer neuropsychological function exhibited slightly better correlations with measures of mental health. Our findings that eye movement function in PCS does not follow the normal recovery path of eye movements after mCHI are indicative of ongoing cerebral impairment. Whilst oculomotor and neuropsychological tests partially overlapped in identifying impairment, eye movements showed additional dysfunction in motor/visuospatial areas, response inhibition, visual attention and subcortical function. Poorer subconscious oculomotor function in the PCS group supports the notion that PCS is not merely a psychological entity, but also has a biological substrate. Measurement of oculomotor function may be of value in PCS cases with a high symptom load but an otherwise unremarkable assessment profile. Routine oculomotor testing should be feasible in centres with existing access to this technology.

Motor deficits and recovery during the first year following mild closed head injury

Objective: This study examined motor impairments over 1 year following mild closed head injury (CHI). It is the first study to serially assess long-term oculomotor and upper-limb visuomotor function following mild head trauma. Methods: Thirty-seven patients with mild CHI and 37 matched controls were compared at 1 week, 3 months and 6 months and 31 available pairs at 12 months post-injury on measures of saccades, oculomotor smooth pursuit, upper-limb visuomotor function and neuropsychological performance. Symptomatic recovery was sampled using the Rivermead Postconcussion Symptoms Questionnaire. Results: At 1 week, the group with CHI reported high levels of post-concussional symptoms and exhibited prolonged saccade latencies, increased directional errors, decreased saccade accuracy and impaired fast sinusoidal smooth pursuit concomitant with increased arm movement reaction time, decreased arm movement speed and decreased motor accuracy on upper-limb visuomotor tracking tasks. Neuropsychological testing identified deficits only in verbal learning and speed of processing while attention, short-term/working memory and general cognitive performance were preserved. At 3 and 6 months, the group with CHI continued to show deficits on several oculomotor and upper-limb visuomotor measures in combination with some deficits on verbal learning and improved, yet abnormal, levels of post-concussional symptoms. At 12 months, the group with CHI had no cognitive impairment but residual deficits in eye and arm motor function and continued to show elevated levels of post-concussional symptoms. Conclusions: The findings indicate that multiple motor systems are measurably impaired up to 12 months following mild CHI and that instrumented motor assessment may provide sensitive and objective markers of cerebral dysfunction during recovery from mild head trauma independent of neuropsychological assessment and patient self-report.

Arterial spin labelling reveals an abnormal cerebral perfusion pattern in Parkinson’s disease

There is a need for objective imaging markers of Parkinsons disease status and progression. Positron emission tomography and single photon emission computed tomography studies have suggested patterns of abnormal cerebral perfusion in Parkinsons disease as potential functional biomarkers. This study aimed to identify an arterial spin labelling magnetic resonance-derived perfusion network as an accessible, non-invasive alternative. We used pseudo-continuous arterial spin labelling to measure cerebral grey matter perfusion in 61 subjects with Parkinsons disease with a range of motor and cognitive impairment, including patients with dementia and 29 age- and sex-matched controls. Principal component analysis was used to derive a Parkinsons disease-related perfusion network via logistic regression. Region of interest analysis of absolute perfusion values revealed that the Parkinsons disease pattern was characterized by decreased perfusion in posterior parieto-occipital cortex, precuneus and cuneus, and middle frontal gyri compared with healthy controls. Perfusion was preserved in globus pallidus, putamen, anterior cingulate and post- and pre-central gyri. Both motor and cognitive statuses were significant factors related to network score. A network approach, supported by arterial spin labelling-derived absolute perfusion values may provide a readily accessible neuroimaging method to characterize and track progression of both motor and cognitive status in Parkinsons disease.

Concussion and mild head injury

A concussion is a physical injury to the head resulting in altered mental function, with expectation of recovery within 2–3 weeks. In a significant minority of cases the symptoms persist longer, thereby comprising a symptom complex commonly referred to as the “post concussion syndrome”, that is, one or more somatic (for example, headaches, dizziness), cognitive (for example, poor concentration, memory), or behavioural/affective (for example, irritability, mood swings) symptoms. Unfortunately, the referral of a patient with the possibility of post concussion syndrome to a busy neurology outpatient clinic can precipitate an inward sigh of reluctant resignation in even the most diligent neurologist or neurosurgeon. We know we are in for a potentially lengthy consultation—long on symptoms and short on signs. Moreover, the process can be convoluted and meandering, as unrewarding for the patient as it is unsatisfying for the clinician. It is important to acknowledge at the outset that there is a dearth of evidence-based knowledge of the underlying pathogenesis, and even less of the best management of post concussive symptoms. Thus, much of the information and advice in this article is empirical and based on expert and personal experience. The terminology surrounding trauma to the head confuses patients, doctors, and lay commentators alike. Terms such as concussion, mild head injury, mild TBI (traumatic brain injury), cerebral concussion, and post concussion syndrome are often used interchangeably to describe the physical injury itself as well as its immediate and later symptomatic consequences. There is in fact no commonly agreed definition of concussion, or whether it even differs from the term mild TBI. Our own working definition is that concussion is an acute trauma-induced change of mental function which generally lasts less than 24 hours (with or without preceding loss of consciousness) and associated with other symptoms (such as headaches and dizziness) which …

Characterizing mild cognitive impairment in Parkinson's disease†

There is growing interest in identifying Parkinsons disease (PD) patients with mild cognitive impairment (PD‐MCI), but widely disparate criteria have been used. We assessed 143 PD patients and 50 matched controls on 20 measures across 4 cognitive domains (executive function, attention and working memory, learning and memory, visuoperception). Twenty‐four patients met criteria for dementia (PD‐D); nondementia patients were classified as either with normal cognition or MCI for 12 neuropsychological criteria. We compared the influence of these criteria on the distribution of global cognitive performance in the resulting PD‐MCI groups relative to the control and PD‐D groups. Different criteria produced substantial variation in the proportion of PD‐MCI cases identified. Fourteen percent PD‐MCI was found when using 2 scores in 1 domain at 2 standard deviations (SD) below normative scores, with no controls identified as MCI, through to 89% PD‐MCI with 1 score in 1 domain at 1 SD below normative scores, when 70% of controls were identified as MCI. The balance of cases with impaired cognition but not those with generally intact cognition was better served by using criteria that required 2 specific deficit scores or deficits across 2 domains. As comparisons with external normative data may have greater applicability across centers, we suggest that 2 scores at −1.5 SD within any single domain (30% PD‐MCI) or 1 score at −1.5 SD in each of 2 domains (37% PD‐MCI) provide suitable criteria to minimize the inclusion of cognitively well patients. Clinical dementia rating did not improve the relative identification of cognitively impaired and unimpaired nondementia PD patients.

Eye movements in patients with neurodegenerative disorders

The neural pathways and brain regions involved in eye movements during ocular fixation and gaze control include the cerebrum, brainstem and cerebellum, and abnormal eye movements can indicate the presence of neurodegeneration. In some patients, oculomotor signs are key to making a diagnosis. Careful clinical examination of eye movements in patients with neurodegenerative disorders is, therefore, an invaluable adjunct to neurological and cognitive assessments. Eye movement recordings in the laboratory are generally not necessary for diagnostic purposes, but can be a useful addition to the clinical examination. Laboratory recordings of eye movements can provide valuable information about disease severity, progression or regression in neurodegenerative disease, and hold particular promise for objective evaluation of the efficacy of putative neuroprotective and neurorestorative therapies. For example, aspects of saccade performance can be tested to probe both motor and cognitive aspects of oculomotor behaviour. This Review describes the oculomotor features of the major age-related movement disorders, including Parkinson disease, Huntington disease, dementia and other neurodegenerative disorders. Findings in presymptomatic individuals and changes associated with disease progression are discussed.

A Pilot Study of Respiration and Swallowing Integration in Parkinson's Disease: ''On'' and ''Off'' Levodopa

Parkinson’s disease is associated with both swallowing and respiratory dysfunction, increasing the risk of aspiration and pneumonia. Previous studies have shown improvements in measurements of swallowing and respiration with levodopa; however, the studies are small and some studies show conflicting reports. The aim of this study was to further investigate the effect of levodopa on respiration. Ten patients with Parkinson’s disease were tested “On” and “Off” levodopa. Assessments included Unified Parkinson’s Disease Rating Scale (UPDRS), coordination of swallowing and respiration, timed-test of swallowing, lung function testing, and, qualitative assessment of swallowing. There was a nonsignificant trend to lower volume per swallow when “On” levodopa, significant reduction in lung function when “On” levodopa, but no difference in coordination of swallowing and respiration or qualitative assessment of swallowing. There was a significant increase in motor examination score of the UPDRS when “Off” levodopa compared to “On.” There may be a reduction in efficiency of swallowing with levodopa medication without any apparent increase in risk of aspiration. These pilot data suggest that further evaluation with larger numbers of participants is justified.

Oculomotor function in multiple system atrophy: Clinical and laboratory features in 30 patients

We reviewed the clinical and laboratory oculomotor features in 30 patients with probable multiple system atrophy (MSA), 22 with MSA‐P and 8 with MSA‐C. Six patients were also examined post mortem, MSA being confirmed in four and excluded in two (Parkinsons disease and progressive supranuclear palsy). Clinical examination showed the following abnormalities; excessive square wave jerks—21 of 30 patients; mild vertical supranuclear gaze palsy—8 of 30; gaze‐evoked nystagmus—12 of 30 patients, three of whom had no extraocular evidence of cerebellar dysfunction; positioning downbeat nystagmus—10 of 25; mild or moderate saccadic hypometria—22 of 30; impaired (“broken up”) smooth pursuit—28 of 30; reduced VOR suppression—16 of 24. Electro‐oculography and caloric testing did not add significant extra information. In patients presenting with an akinetic‐rigid syndrome it can be difficult to differentiate idiopathic Parkinsons disease from MSA‐P and other causes of atypical parkinsonism. Our findings suggest that the presence of excessive square wave jerks, mild – moderate hypometria of saccades, impaired VOR suppression, spontaneous nystagmus or positioning downbeat nystagmus may be oculomotor “red flags” or clues to the presence of MSA. Further, the presence of clinically slow saccades, or moderate‐to‐severe gaze restriction, suggests a diagnosis other than MSA.