Perverted Head-Shaking and Positional Downbeat Nystagmus in Essential Tremor

Even though the pathophysiology is not completely understood, cerebellar dysfunction has been invoked in essential tremor (ET). We evaluated cerebellar dysfunction in ET with the presence of perverted head-shaking (pHSN) and positional downbeat nystagmus (pDBN) which are known to reflect cerebellar dysfunction. First, we reviewed the videooculography (VOG) of 185 patients with ET from March 2007 to April 2010. Seventeen of 28 patients with pHSN and pDBN were followed up for at least a 1.8-year interval from baseline to determine the clinical course. And then, we recruited 52 consecutive patients with ET and compared their ocular motor findings with 51 normal controls using VOG. Among the 185 patients with ET, 28 (15.1 %) showed pHSN (n?=?23, 12.4 %) or pDBN (n?=?8, 4.3 %). Seventeen of them who were followed up did not develop Parkinsonism or other neurologic deficits during the observation period. The subsequent case-control study showed a higher prevalence of pHSN or pDBN (11/52, 21.2 %, pHSN in nine and pDBN in five) in patients with ET than in the normal controls (2/51, 3.9 %, pHSN only, P?=?0.015). The tremor rating scale or involved body sites did not differ between the patients with and without pHSN/pDBN. pHSN and pDBN were more common in patients with ET than in the normal controls. This result supports that cerebellar dysfunction is associated with ET.     

Ocular motor characteristics of different subtypes of spinocerebellar ataxia: Distinguishing features

Because of frequent involvement of the cerebellum and brainstem, ocular motor abnormalities are key features of spinocerebellar ataxias and may aid in differential diagnosis. Our objective for this study was to distinguish the subtypes by ophthalmologic features after head‐shaking and positional maneuvers, which are not yet recognized as differential diagnostic tools in most common forms of spinocerebellar ataxias. Of the 302 patients with a diagnosis of cerebellar ataxia in 3 Korean University Hospitals from June 2011 to June 2012, 48 patients with spinocerebellar ataxia types 1, 2, 3, 6, 7, or 8 or with undetermined spinocerebellar ataxias were enrolled. All patients underwent a video‐oculographic recording of fixation abnormalities, gaze‐evoked nystagmus, positional and head‐shaking nystagmus, and dysmetric saccades. Logistic regression analysis controlling for disease duration revealed that spontaneous and positional downbeat nystagmus and perverted head‐shaking nystagmus were strong predictors for spinocerebellar ataxia 6, whereas saccadic intrusions and oscillations were identified as positive indicators of spinocerebellar ataxia 3. In contrast, the presence of gaze‐evoked nystagmus and dysmetric saccades was a negative predictor of spinocerebellar ataxia 2. Positional maneuvers and horizontal head shaking occasionally induced or augmented saccadic intrusions/oscillations in patients with spinocerebellar ataxia types 1, 2, and 3 and undetermined spinocerebellar ataxia. The results indicated that perverted head‐shaking nystagmus may be the most sensitive parameter for SCA6, whereas saccadic intrusions/oscillations are the most sensitive for spinocerebellar ataxia 3. In contrast, a paucity of gaze‐evoked nystagmus and dysmetric saccades is more indicative of spinocerebellar ataxia 2. Head‐shaking and positional maneuvers aid in defining ocular motor characteristics in spinocerebellar ataxias. © 2013 Movement Disorder Society     

Impaired Tilt Suppression of Post-Rotatory Nystagmus and Cross-Coupled Head-Shaking Nystagmus in Cerebellar Lesions: Image Mapping Study

We sought to determine the cerebellar structures responsible for tilt suppression of post-rotatory nystagmus. We investigated ocular motor findings and MRI lesions in 73 patients with isolated cerebellar lesions who underwent recording of the vestibulo-ocular reflex (VOR) using rotatory chair tests. Tilt suppression of post-rotatory nystagmus was diminished in 27 patients (27/73, 37.0 %). The gains of the VOR and the TCs of per- and post-rotatory nystagmus did not differ between the patients with diminished and with normal tilt suppression. The patients with impaired tilt suppression showed perverted (“cross-coupled”) head-shaking nystagmus (pHSN) and central positional nystagmus (CPN) more frequently than those with normal responses. Tilt suppression was impaired in five (71.4 %) of the seven patients with isolated nodulus and uvular infarction. Probabilistic lesion-mapping analysis showed that the nodulus and uvula are responsible for tilt suppression. Impaired tilt suppression may be ascribed to disruption of cerebellar contribution to the vestibular velocity-storage mechanism, which integrates information from the semicircular canals and otolith organs to help derive the brain’s estimate of the head orientation relative to the pull of gravity.     

Positional down beating nystagmus in 50 patients: cerebellar disorders and possible anterior semicircular canalithiasis

OBJECTIVES: To clarify the clinical significance of positional down beat nystagmus (pDBN). METHODS: A discussion of the neuro-otological findings in 50 consecutive patients with pDBN. RESULTS: In 38 patients there was evidence of CNS disease (central group) but in 12 there was not (idiopathic group). In the CNS group, presenting symptoms were gait, speech, and autonomic dysfunction whereas in the idiopathic group patients mostly reported positional vertigo. The main neurological and oculomotor signs in the CNS group were explained by cerebellar dysfunction, including 13 patients with multiple system atrophy. In patients with multiple system atrophy with a prominent extrapyramidal component, the presence of pDBN was helpful in the differential diagnosis of atypical parkinsonism. No patient with pDBN had the Arnold-Chiari malformation, a common cause of constant down beat nystagmus (DBN). In the idiopathic group, the pDBN had characteristics which suggested a peripheral labyrinthine disorder: vertigo, adaptation, and habituation. In six patients an additional torsional component was found (concurrently with the pDBN in three). Features unusual for peripheral disorder were: bilateral positive Dix-Hallpike manoeuvre in nine of 12 patients and selective provocation by the straight head-hanging manoeuvre in two. CONCLUSION: It is argued that some patients with idiopathic pDBN have benign paroxysmal positional vertigo (BPPV) with lithiasis of the anterior canal. The torsional component may be weak, because of the predominantly sagittal orientation of the anterior canal, and may not be readily seen clinically. Nystagmus provocation by bilateral Dix-Hallpike and straight head-hanging may be explained by the vertical upwards orientation of the ampullary segment of the anterior canal in the normal upright head position. Such orientation makes right-left specificity with the Dix-Hallpike manoeuvre less important than for posterior canal BPPV. This orientation requires a further downwards movement of the head, often achieved with the straight head-hanging position, to provoke migration of the canaliths. The straight head-hanging manoeuvre should be carried out in all patients with a history of positional vertigo and a negative Dix-Hallpike manoeuvre.     

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 (Parkinson's 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 Parkinson's 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. © 2008 Movement Disorder Society     

后循环梗死患者的眼动及前庭功能评价

目的   评价眼动及前庭功能检查对后循环梗死（posterior circulation Infarction,PCI）患者的诊断价值。 方法  纳入22例PCI患者,收集其临床基线资料,包括性别、年龄、首发症状、高血压、糖尿病、吸烟、饮酒史及入院体征等相关指标。患者均行眼动检查：包括凝视试验（gaze test,GT）、扫视试验（saccade test,ST）、平滑跟踪试验（smooth pursuit test,SPT）、视动眼震检查（optokinetic nystagmus test,OPK）;前庭功能检查：包括自发眼震（spontaneous nystagmus,SN）、摇头试验（head shaking test,HST）、固视抑制检查,上述检查均应用眼震视图仪（videonystagmograph,VNG）进行记录。 结果  共纳入22例PCI患者,首发症状：15例（68.2%）为头晕/眩晕,7例（31.8%）为肢体无力麻木。眼动检查提示：异常19例（86.4%）,其中GT异常4例（18.2%）,ST异常11例（50.0%）,SPT异常15例（68.2%）,OPK异常12例（54.5%）。前庭功能检查提示：22例完成SN检查,其中SN阳性8例（36.4%）,包括小脑梗死4例,脑桥梗死3例,左侧延髓背外侧、双侧小脑半球及蚓部梗死1例;17例完成HST检查,其中HST阳性6例（35.3%）,包括小脑梗死2例,脑桥梗死2例,小脑及脑桥梗死1例,右侧小脑及延髓上段梗死1例;19例完成固视抑制检查,其中固视抑制失败8例（42.1%）,包括双侧小脑梗死1例,脑桥梗死4例,左侧延髓梗死1例,右侧小脑及延髓上段梗死1例,左侧延髓背外侧、双侧小脑半球及蚓部梗死1例。以头晕/眩晕为首发症状的患者与以肢体无力、麻木为首发症状的患者相比,眼动及固视抑制检查阳性率高（P分别为0.023和0.045）。 结论  小脑、延髓梗死的患者常以头晕/眩晕起病;眼动检查有助于筛查PCI患者;小脑梗死患者的病灶侧别常与自发、摇头眼震的水平成分一致;脑桥梗死患者HST后可诱发下跳眼震;脑桥、延髓梗死患者常固视抑制失败。     

Application of the International Cooperative Ataxia Scale rating in multiple system atrophy.

We assessed the International Cooperative Ataxia Scale (ICARS) as a means of extracting and rating cerebellar signs in multiple system atrophy (MSA). Cross-sectional analysis of internal consistency, factor structure, and correlation with parkinsonism severity (Unified Parkinson's Disease Rating Scale [UPDRS] III) of the ICARS, in 50 unselected MSA patients (mean age, 67.6 years; mean disease duration, 5.5 years), 50 age-matched and disease duration-matched Parkinson' disease (PD) patients, and 50 control subjects. Fifteen patients (30%) had MSA-C (cerebellar subtype) and 35 (70%) MSA-P (parkinsonism subtype), and 66% had at least one cerebellar sign. The total ICARS score was much higher (fivefold) in MSA compared to PD patients. The ICARS score was twofold higher in MSA-C than in MSA-P patients. MSA-C patients had a higher score than MSA-P mainly on posture and gait disturbances and kinetic functions subscores. All the ICARS items were significantly more severe in MSA than in PD patients, who in turn scored higher than the controls. In MSA, internal consistency was excellent (Cronbach = 0.93). Factor structure analysis revealed four clinically distinct subscores, in accordance with the scale structure, which accounted for 70% of the variance. The ICARS showed less consistency and accuracy in PD patients; however, the ICARS scores significantly correlated with the UPDRS-III scores in both MSA and PD patients. The ICARS appears a useful tool to extract and rate the severity of cerebellar signs in MSA; however, it is clearly contaminated by parkinsonian features.     

Multiple system atrophy is distinguished from idiopathic Parkinson's disease by the arginine growth hormone stimulation test

OBJECTIVE: Multiple system atrophy (MSA) may be difficult to distinguish from idiopathic Parkinson's disease (PD). Our aim was to evaluate the accuracy of the arginine growth hormone (GH) stimulation test in distinguishing between MSA and PD in large populations of patients. METHODS: We measured the GH response to arginine in 69 MSA (43 MSAp [parkinsonism as the main motor feature] and 26 MSAc [cerebellar features predominated]) patients, 35 PD patients, and 90 healthy control subjects. We used receiver-operating curve analysis to establish the arginine cutoff value that best differentiated between MSA and PD. RESULTS: The GH response to arginine was significantly lower (p < 0.01) in MSA than in either PD patients or control subjects. At a cutoff level of 4 microg/L, arginine distinguished MSAp from PD with a sensitivity and specificity of 91% and MSAc from PD with a sensitivity of 96% and specificity of 91%. The arginine test had a positive predictive value for MSA of 95%. The GH response to arginine was not affected by disease duration or severity, MSA motor subtype, pyramidal signs, response to dopaminergic therapy, or magnetic resonance imaging findings. INTERPRETATION: The GH response to arginine differentiates MSA from PD with a high diagnostic accuracy. The results suggest an impairment of cholinergic central systems modulating GH release in MSA.     

Vertigo and vestibular abnormalities in spinocerebellar ataxia type 6

Spinocerebellar ataxia type 6 (SCA6) is a calcium channelopathy due to a pathological CAG repeat expansion in CACNL1A4. Patients frequently describe paroxysmal vertigo early in the disease course, but it is not clear whether this is central or labyrinthine in origin. To address this issue we studied 21 SCA6 patients. Symptoms of vertigo were defined using a structured questionnaire. Signs were recorded during a standardised bed-side vestibular examination that included systematic positional testing with Frenzel goggles. Brief, recurrent attacks of vertigo occurred in 13 patients, usually preceding the onset of ataxia. Nystagmus was observed behind Frenzel goggles in 14 patients, and was induced either during positional testing, or head shaking in 20 patients. Only one patient had findings typical of benign paroxysmal positional vertigo (BPPV). Combined downbeat and horizontal gaze-evoked nystagmus (“side-pocket”) was the most common form, occurring most commonly in supine and head-hanging positions, and following horizontal head-shaking. Nystagmus beating away from the ground (apogeotropic) occurred in 9 patients as they lay on their side. In conclusion, vertigo and abnormalities on bedside vestibular examination are common in SCA6, with forms of nystagmus typical of cerebellar, rather than labyrinthine, disease. These findings demonstrate phenotypic overlap between SCA6 and episodic ataxia type 2, which are both due to mutations in CACNL1A4.     

Limb Shaking Transient Ischemic Attacks with Normal Neurovascular Ultrasound may Herald Cardioembolic Stroke: A Case Report

Our objective is to highlight that the rare occurrence of limb shaking in transient ischemic attacks may be underpinned by etiologies other than critical internal carotid stenosis/occlusion. We describe a 74 year-old woman with abrupt left arm jerking and normal urgent computed tomography scan, electroencephalography (EEG) as well as carotid and transcranial ultrasound. Two days later she developed an overt ischemic stroke, with left mesencephalon and left cerebellar hemisphere lesions at brain magnetic resonance imaging and paroxysmal atrial fibrillation at Holter-EKG. Transient ischemic attacks should be considered in the differential diagnosis of limb shaking even in patients with normal carotid and transcranial ultrasonography.     

Individual voxel-based morphometry adjusting covariates in multiple system atrophy

IntroductionThis study aimed to evaluate whether novel individual voxel-based morphometry adjusting covariates (iVAC), such as age, sex, and total intracranial volume, could increase the accuracy of a diagnosis of multiple system atrophy (MSA) and enable the differentiation of MSA from Parkinson's disease (PD).MethodsWe included 53 MSA patients (MSA-C: 33, MSA-P: 20), 53 PD patients, and 189 healthy controls in this study. All participants underwent high-resolution T1-weighted imaging (WI) and T2-WI with a 3.0-T MRI scanner. We evaluated the occurrence of significant atrophic findings in the pons/middle cerebellar peduncle (MCP) and putamen on iVAC and compared these findings with characteristic changes on T2-WI.ResultsOn iVAC, abnormal findings were observed in the pons/MCP of 96.2% of MSA patients and in the putamen of 80% of MSA patients; however, on T2-WI, they were both observed at a frequency of 60.4% in MSA patients. On iVAC, all but one MSA-P patient (98.1%) showed significant atrophic changes in the pons/MCP or putamen. By contrast, 69.8% of patients with MSA showed abnormal signal changes in the pons/MCP or putamen on T2-WI. iVAC yielded 95.0% sensitivity and 96.2% specificity for differentiating MSA-P from PD.ConclusioniVAC enabled us to recognize the morphological characteristics of MSA visually and with high accuracy compared to T2-WI, indicating that iVAC is a potential diagnostic screening tool for MSA.     

Apparent diffusion coefficient of the superior cerebellar peduncle differentiates progressive supranuclear palsy from Parkinson's disease

The early diagnosis of progressive supranuclear palsy (PSP) may be challenging, because of clinical overlapping features with Parkinson's disease (PD) and other parkinsonian syndromes such as the Parkinsonian variant of multiple system atrophy (MSA‐P). Conventional MRI can help in differentiating parkinsonian disorders but its diagnostic accuracy is still unsatisfactory. On the basis of the pathological demonstration of superior cerebellar peduncle (SCP) atrophy in patients with PSP, we assessed the SCP apparent diffusion coefficient (ADC) values in patients with PSP, PD, and MSA‐P in order to evaluate its differential diagnostic value in vivo. Twenty‐eight patients with PSP (14 with possible‐PSP and 14 with probable‐PSP), 15 PD, 15 MSA‐P, and 16 healthy subjects were studied by using diffusion weighted imaging (DWI). ADC was calculated in regions of interest defined in the left and right SCP by two clinically blinded operators. Intrarater (r = 0.98, P < 0.001) and interrater reliability (r = 0.97; P < 0.001) for SCP measurements were high. Patients with PSP had higher SCP rADC values (median 0.98 × 10^?3mm²/s) than patients with PD (median 0.79 × 10^?3 mm²/s, P < 0.001), MSA‐P (median 0.79 × 10^?3 mm²/s, P < 0.001), and healthy controls (median 0.80 × 10^?3 mm²/s, P < 0.001). DWI discriminated patients with PSP from PD and healthy subjects on the basis of SCP rADC individual values (100% sensitivity and specificity) and from patients with MSA‐P (96.4% sensitivity and 93.3% specificity). The higher values of rADC in SCP of patients with PSP correspond with the in vivo microstructural feature of atrophy detected postmortem and provide an additional support for early discrimination between PSP and other neurodegenerative parkinsonisms. © 2008 Movement Disorder Society     

Diagnostic value of brain MRI and 18F‐FDG PET in the differentiation of parkinsonian type multiple system atrophy from Parkinson’s disease

Background and purpose: Differentiation between parkinsonian type multiple system atrophy (MSA‐P) and Parkinson’s disease (PD) is important but often difficult. We investigated the diagnostic value of brain magnetic resonance imaging (MRI) and ¹⁸F‐fluorodeoxyglucose positron emission tomography (¹⁸F‐FDG PET) in differentiating MSA‐P from PD. Methods: Twenty‐four patients with MSA‐P (16 probable and 8 possible) and eight patients with PD were included in this study. Results: For analysis using the putaminal findings, the sensitivities were 58.3% by visual analysis of brain MRI, 95.8% by visual analysis of ¹⁸F‐FDG PET, and 79.2% by statistical parametric mapping (SPM) analysis of ¹⁸F‐FDG PET in differentiating MSA‐P from PD; the specificity was 100% for each analysis. Using the putaminal findings, visual analysis of ¹⁸F‐FDG PET had a higher sensitivity compared with brain MRI (P = 0.004) and SPM analysis of ¹⁸F‐FDG PET revealed a tendency towards higher sensitivity compared with brain MRI (P = 0.063). For analysis using both putaminal and infratentorial findings, the sensitivities were 79.2% by visual analysis of brain MRI, 95.8% by visual analysis of ¹⁸F‐FDG PET, 95.8% by SPM analysis of ¹⁸F‐FDG PET in differentiating MSA‐P from PD; the specificity was 100% for each analysis. Conclusion: Both brain MRI and ¹⁸F‐FDG PET showed diagnostic usefulness in differentiating MSA‐P from PD, with ¹⁸F‐FDG PET being more sensitive than brain MRI.     

Isolated horizontal positional nystagmus from a posterior fossa lesion

Isolated vertigo with horizontal positional nystagmus as an impending sign of a central lesion has rarely been reported. Here we present neuro‐otologic findings of patients with these clinical signs. Lesion overlays from 6 patients with ageotropic positional nystagmus revealed that the nodulus and vermis are common areas of injury. In contrast, 2 patients with geotropic positional nystagmus had cerebellar peduncle and lateral medullary lesions. These clinical findings suggest that vertigo with horizontal positional nystagmus, even in the absence of other initial neurological signs, may indicate a posterior fossa lesion, including that in the nodulus, vermis, and deep cerebellar structures. Ann Neurol 2014;76:905–910     

Natural course of positional down-beating nystagmus of peripheral origin

The aim of this study was to assess the natural course of positional down-beating nystagmus (pDBN) and vertigo in patients with no evidence of central nervous system involvement and of presumed peripheral origin. Fifty-three patients with pDBN had a complete otoneurological examination. All subjects, apart from three (excluded from the study), showed no additional neurological signs and normal brain imaging. Patients were randomly assigned to two groups: with or without treatment with exercise. Patients were seen again after 24 h, and then weekly for up to 6 months. Forty-seven patients (94 %) showed pDBN in the straight head-hanging position and in a Dix–Hallpike position. A torsional component was detected in 17 patients (34 %). The mean latency and duration of pDBN was 4.7 ± 5 s and 40.1 ± 22 s, respectively. After 2 weeks, only 12 patients (24 %) still had pDBN and all but one patient had recovered by 1 month. Twenty patients (40 %) were diagnosed with a typical posterior canal benign paroxysmal positional vertigo (PC BPPV) before or after pDBN. This study assessed for the first time the natural course of presumed peripheral pDBN, which was characterized by a spontaneous remission in 24 patients in the first week and in 49 patients within 4 weeks. pDBN is much more common than previously suggested, with about the same frequency as lateral canal BPPV. Furthermore, the clinical characteristics of pDBN have been highlighted, as well as its possible relationship to PC BPPV.     

Apogeotropic central positional nystagmus as a sole sign of nodular infarction

Positional vertigo and nystagmus without associated neurological symptoms and signs are characteristic features of benign paroxysmal positional vertigo (BPPV). Although positional nystagmus may occur with caudal cerebellar infarction including the nodulus, positional nystagmus is usually associated with other neurological signs such as spontaneous or gaze-evoked nystagmus, perverted head-shaking nystagmus, cerebellar dysmetria, or severe gait ataxia with falling. We present a patient with nodular infarction who had positional vertigo with nystagmus as a sole manifestation. Video-oculography showed apogeotropic positional horizontal nystagmus during head turning while supine, which was consistent with apogeotropic BPPV involving the horizontal canal. MRI disclosed acute infarct in the nodulus. Nodulus infarction should be considered in a patient with positional nystagmus, especially when the presenting symptoms and signs are consistent with BPPV involving the horizontal canal.     

What features improve the accuracy of the clinical diagnosis of progressive supranuclear palsy‐parkinsonism (PSP‐P)?

Progressive supranuclear palsy‐parkinsonism (PSP‐P) is a primary tauopathy characterised by neurofibrillary degeneration, which is frequently mistaken for Parkinson's disease (PD), multiple system atrophy (MSA), and vascular parkinsonism (VP) at presentation. The aim of this study was to identify particular clinical features (green flags) that may be helpful in differentiating PSP‐P from these other disorders. We identified 37 patients with PSP‐P from 726 patients archived at the Queen Square Brain Bank. Using a retrospective case notes review the clinical features were compared between the PSP‐P group and Lewy body associated parkinsonism (PD, n = 444 and dementia with Lewy bodies (DLB), n = 46), MSA (n = 90), and VP (n = 19), using the χ²‐test for proportions for a two‐by‐two contingency table. The sensitivity, specificity, and positive predictive values (PPV) and negative predictive values (NPV) were calculated for individual clinical features. A specificity of >0.85 or a PPV of >0.85 were considered reliable discriminators. No clinical features were predictive of PSP‐P, but late drug induced dyskinesias (specificity 0.92, PPV 0.99), late autonomic dysfunction (specificity 0.94, PPV 0.99) and any visual hallucinations (specificity 0.94, PPV 0.99) were better in distinguishing PD and PSP‐P than predicted using operational diagnostic criteria for PD. PSP‐P shares many clinical features with PD and DLB, MSA and VP, but visual hallucinations, drug induced dyskinesias and autonomic dysfunction are very uncommon and may be helpful exclusion criteria. © 2010 Movement Disorder Society     

An autopsy case of preclinical multiple system atrophy (MSA‐C)

Multiple system atrophy (MSA) is divided into two clinical subtypes: MSA with predominant parkinsonian features (MSA‐P) and MSA with predominant cerebellar dysfunction (MSA‐C). We report a 71‐year‐old Japanese man without clinical signs of MSA, in whom post mortem examination revealed only slight gliosis in the pontine base and widespread occurrence of glial cytoplasmic inclusions in the central nervous system, with the greatest abundance in the pontine base and cerebellar white matter. Neuronal cytoplasmic inclusions (NCIs) and neuronal nuclear inclusions (NNIs) were almost restricted to the pontine and inferior olivary nuclei. It was noteworthy that most NCIs were located in the perinuclear area, and the majority of NNIs were observed adjacent to the inner surface of the nuclear membrane. To our knowledge, only four autopsy cases of preclinical MSA have been reported previously, in which neuronal loss was almost entirely restricted to the substantia nigra and/or putamen. Therefore, the present autopsy case of preclinical MSA‐C is considered to be the first of its kind to have been reported. The histopathological features observed in preclinical MSA may represent the early pattern of MSA pathology.     

Acquired pendular nystagmus in multiple sclerosis: clinical observations and the role of optic neuropathy.

Thirty seven patients with pendular nystagmus due to multiple sclerosis were reviewed. Most developed nystagmus later in a progressive phase of the disease. All had cerebellar signs on examination and evidence of optic neuropathy. MRI in eight patients showed cerebellar or brainstem lesions in seven; the most consistent finding was a lesion in the dorsal pontine tegmentum. Dissociated nystagmus was seen in 18 patients: in these the signs of optic neuropathy were often asymmetric and the severity correlated closely with the side with larger oscillations. This suggests that dissociations in acquired pendular nystagmus may be due to asymmetries in optic neuropathy rather than asymmetries in cerebellar or brainstem disease.     

Cardiovascular dysautonomia in Parkinson's disease and multiple system atrophy

OBJECTIVES: To determine whether Parkinson's disease (PD) can be distinguished from multiple system atrophy (MSA) on the basis of the assessment of iodine-123 meta-iodobenzylguanidine (123I-MIBG) radioactivity in heart and cardiovascular autonomic function. PATIENTS AND METHODS: Seventeen patients with MSA, 39 with PD, and 25 healthy volunteers underwent 123I-MIBG scintigraphy and hemodynamic autonomic function tests using Valsalva maneuver (VM). Baroreceptor reflex sensitivity (BRS) was measured using the slope of the relation between RR interval and blood pressure during the fourth phase. RESULTS: 123I-MIBG radioactivity in heart of patients with PD was lower than that of control subjects and patients with MSA, but there was some overlap between PD and MSA. BRS in patients with PD who had a 123I-MIBG radioactivity similar to that in MSA was larger than that in patients with MSA, with no overlap in any patient. CONCLUSION: Assessment of BRS may be useful for differentiating between MSA and PD that had a 123I-MIBG radioactivity similar to MSA.