Camptocormia or Pisa syndrome in multiple system atrophy

Although a mild stooped posture is a hallmark of parkinsonism, extreme trunk forward flexion is not common. This phenomenon was described in different etiological entities and called camptocormia. Other similar presentations called Pisa syndrome and antecollis were described mainly in extrapyramidal disorders. Authors present two cases of probable multiple system atrophy (MSA) with predominant parkinsonism and Pisa syndrome (or camptocormia). Both of them were previously misdiagnosed as idiopathic Parkinson's disease (PD) and one was reported 1 year earlier. The typical clinical presentation fulfilling the diagnostic criteria for multiple system atrophy, rapid progression with lack of responsiveness to L-DOPA and apomorphine and typical MRI putaminal pathology observed in both cases allowed us to make a diagnosis. Accuracy of clinical diagnosis in multiple system atrophy is still very poor. Therefore, unusual or rare clinical presentations may support the final diagnosis. The camptocormia, Pisa syndrome and antecollis may represent the continuum of the same motor phenomenon and most of the authors refer them to unusual form of axial dystonia. According to many clinical presentations on different forms of camptocormia/Pisa syndrome authors conclude that not etiology, but the localization of specific lesion, probably within putamen is responsible for that form of dystonia. In cases of parkinsonism and severe forward flexion of trunk multiple system atrophy, diagnosis should be considered.     

Comparison of cerebral atrophy evaluated by MRI in Parkinson's disease and multiple system atrophy

Cerebral atrophy was evaluated in 31 patients with Parkinson's disease (PD) and 24 patients with clinically probable multiple system atrophy (MSA). Measurements of ventricular and brainstem areas, obtained from axial and sagittal MRI sections, were performed using a computer digitalizing system. Cortical and cerebellar atrophies were subjectively assessed. All measures were scored by one observer who was blind to the diagnosis (BD). Age, sex, levodopa dosage, baseline motor Parkinsonian disability (i.e. without levodopa treatment) and neuropsychological impairment were not significantly different between the two groups of patients. The total brainstem area (p < 0.001), the mesencephalon (p < 0.05) and the pons (p = 0.05) areas were significantly smaller in MSA as were the lobar (p < 0.05) and the vermian (p < 0.01) parts of the cerebellum. In the MSA group, significant correlations were observed between the brainstem area and items from the motor part of the Unified Parkinson's Disease Rating Scale (dysarthria, posture, arising from a chair), and between the cerebellar atrophy and the gait disturbance. A progressive discriminant analysis using radiologic variables correctly classified 79% of patients in their own diagnosis group with a significant difference (p = 0.01). From these results, it appears that MRI could help to differentiate MSA from PD, especially when MRI detects a severe infratentorial atrophy suggestive of MSA. However, brainstem and cerebellum atrophies are not sufficient criteria to differentiate MSA from PD because they lack both specificity and sensitivity.     

Metaiodobenzylguanidine (MIBG) scintigraphy at various parts of the body in Parkinson's disease and multiple system atrophy

We compared MIBG uptake at various parts of the body in controls and patients with Parkinson's disease and multiple system atrophy. In the heart, MIBG uptake in Parkinson's disease (early H/M: 1.668+/-0.325, late H/M: 1.500+/-0.402) was less than that in multiple system atrophy (early H/M: 2.395+/-0.186, late H/M: 2.530+/-0.391) and controls (early H/M: 2.635+/-0.508, late H/M: 2.575+/-0.635) (early: P<0.0001, late: P<0.0001). There were no significant differences in uptake by the lung, thyroid, or liver in the three groups. Only on early images, uptake in the shoulder in multiple system atrophy (early S/M: 0.473+/-0.78) and Parkinson's disease (early S/M: 0.470+/-0.710) was decreased compared to that in controls (early S/M: 0.560+/-0.118) (P=0.0252). MIBG is reported to be taken up in the terminal part of sympathetic nerves and demonstrates sympathetic nerve activity, especially on late images. The cause of differences between the heart and other parts of the body remains unknown. We consider the following possibilities: (a) differences in the sympathetic nervous system between Parkinson's disease and multiple system atrophy are more subtle in organs other than the heart; (b) the cause of MIBG uptake reduction by the heart in Parkinson's disease involves factors in addition to sympathetic nervous system damage; and (c) MIBG uptake by organs other than the heart involves not only the sympathetic nervous system but also non-neuronal components. In conclusion, MIBG uptake by organs other than the heart cannot differentiate Parkinson's disease from multiple system atrophy at present.     

Presynaptic parkinsonism in multiple system atrophy mimicking Parkinson's disease: a clinicopathological case study.

We describe the clinicopathological findings in a patient aged 63 years at death who, at age 55 years, developed levodopa-responsive parkinsonism with no atypical features. A diagnosis of idiopathic Parkinson's disease (PD) was made. During the clinical course, fluctuations and dyskinesias appeared. Eight years after onset, he was successfully treated with subthalamic nucleus stimulation but died 3 weeks postoperatively from pulmonary embolus. Brain autopsy showed marked neuronal loss and gliosis in the substantia nigra and locus coeruleus, and, to a much lesser extent, in the basis pontis, inferior olivary nuclei, and cerebellar cortex. Striatum was normal. There were numerous oligodendroglial and neuronal cytoplasmic inclusions and neuropil threads, the highest density being localized in the pons and cerebellar white matter. No Lewy bodies were observed. We conclude that nigral, presynaptic parkinsonism may occur in multiple system atrophy, which even in the long run can be indistinguishable from PD. Putaminal preservation accounts for good response to both levodopa therapy and subthalamic nucleus stimulation.     

Cerebrospinal fluid myelin basic protein is elevated in multiple system atrophy

IntroductionParkinson's disease (PD) and multiple system atrophy (MSA) have overlapping symptoms, challenging an early diagnosis. Diagnostic accuracy is important because PD and MSA have a different prognosis and response to treatment. Here, we aimed to evaluate the diagnostic value of brain-specific structural proteins in cerebrospinal fluid (CSF) of PD and MSA patients, as well as their association with cognitive decline.MethodsCSF samples were collected from patients with clear signs of parkinsonism, but with uncertain diagnosis at the time of inclusion. Clinical diagnoses of PD (n = 55) and MSA (n = 22) were established after 3 and 10 years of follow-up and re-evaluated after 12 years, according to the most updated clinical criteria. CSF from controls (n = 118) was studied for comparison. Neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP), S100 calcium-binding protein B (S100B) and myelin basic protein (MBP) levels in CSF were measured using ELISA. Protein levels were also correlated with cognitive decline, i.e. worsening of the mini mental state examination (MMSE) over a period of three years.ResultsMBP concentrations were increased in MSA compared to PD and controls (p < 0.005) and could differentiate MSA and PD with high accuracy (AUC = 0.781; p < 0.001). Concentrations of MPB, GFAP and S100B, but not NSE, were significantly elevated in PD patients compared to controls (p = 0.05). None of the brain-specific structural proteins correlated with MMSE progression.ConclusionsOur results demonstrate that MBP differentiates PD from MSA at early stages of the disease, indicating that demyelination and axonal damage may already occur in early stages of MSA.     

Clinical correlates of serum insulin-like growth factor-1 in patients with Parkinson's disease,multiple system atrophy and progressive supranuclear palsy

BackgroundRecently, increased serum insulin-like growth factor-1 (IGF-1) levels have been reported in patients with Parkinson's disease (PD) and multiple system atrophy (MSA).ObjectiveTo assess a correlation between the serum IGF-1 levels and clinical background factors in patients with PD and related disorders such as MSA and progressive supranuclear palsy (PSP).MethodsA total of 79 PD patients, 25 MSA patients, 16 PSP patients and 52 healthy controls were included in this study. The serum IGF-1 and growth hormone (GH) levels were measured in a fasting state. Unified PD Rating Scale (UPDRS) part III was used to evaluate motor function. Unified MSA Rating Scale (UMSARS) part II was also employed for the MSA patients.ResultsThe serum IGF-1 levels were significantly increased in the MSA patients compared with the PD patients and controls. No significant differences were observed in the serum GH levels among the patients and controls. The serum IGF-1 levels of PD patients with Hoehn and Yahr stage 2 were significantly higher than those of patients with Hoehn and Yahr stages 3–5. In patients with PD and PSP, the serum IGF-1 levels were negatively correlated with UPDRS part III. In contrast, patients with MSA showed a positive correlation of the serum IGF-1 levels with disease duration, UPDRS part III and UMSARS part II.ConclusionThe difference in the serum IGF-1 level and its correlation with clinical variables among these disorders may reflect different ongoing disease processes in each disorder.     

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.     

Topographic distribution of cortical thinning in subtypes of multiple system atrophy

Background and purposeDespite the predominant degeneration of subcortical structures, recent studies have suggested the evidence of cortical involvement in multiple system atrophy (MSA). This study aimed to identify the different topographic pattern of cortical thinning in MSA according to clinical subtypes, and the association of cortical thinning with cerebellar atrophy and other disease related metrics.Materials and methodsWe used cortical thickness analysis in 53 non-demented probable MSA patients (29 with MSA-C, 24 with MSA-P) and 35 healthy subjects and modeled local cortical thickness as a linear association with cerebellar volume and disease related metrics including age, disease duration, cognition and disease severity.ResultsWe found five clusters (left ventromedial prefrontal, bilateral ventrolateral prefrontal cortex, right parahippocampal and lingual gyrus) exhibiting significant cortical thinning in MSA-C and two clusters (right primary sensory motor and left ventromedial prefrontal cortex) exhibiting a thinning tendency in MSA-P compared with the control group. In correlation analysis, we identified no cluster exhibiting a significant correlation with cerebellar atrophy in both of the MSA groups. However, cortical thickness in right parahippocampalgyrus and left ventrolateral prefrontal cortex showed significant negative correlation with International Cooperative Ataxia Rating Scale subscore of speech disorder in MSA-C group.ConclusionsWe identified different topographic distributions of cortical thinning in MSA subtypes. Our study suggests that cortical thinning of MSA occurs independently of cerebellar atrophy as a primary disease process rather than secondary deafferentation.     

Sphincter electromyography and multiple system atrophy

Electromyographic studies of the sphincter in patients with multiple system atrophy have shown increased duration and polyphasia of motor unit potentials. These electrophysiological markers have been used to argue for the selective degeneration of sacral motor neurons in Onuf's nucleus in patients with multiple system atrophy. Studies comparing sphincter electromyographic changes in patients with multiple system atrophy and Parkinson's disease have shown significant differences between these two patient populations. Despite the controversy surrounding this claim, recent studies using quantitative electromyographic techniques support the view that reinnervation of the anal sphincter muscles may be a useful diagnostic marker for distinguishing multiple system atrophy from Parkinson's disease. A critical review of these data is needed to assess the validity and reliability of electromyographic changes in multiple system atrophy.     

Putaminal magnetic resonance imaging features at various magnetic field strengths in multiple system atrophy

We delineated the effects of magnetic field strength on signal intensities to facilitate the specific findings of multiple system atrophy (MSA). Fifteen patients with probable MSA were imaged by 0.35T fast spin‐echo (FSE), 1.5T FSE, and 3.0T FSE using a consistent protocol, testing all field strengths on the same day. Sixty patients with probable Parkinson's disease (PD) also underwent imaging. Moderate or marked hyperintensity at the dorsolateral outer putaminal margin, hyperintensity of the putaminal body, hypointensity relative to the globus pallidus at the dorsolateral putaminal margin, and infratentorial signal changes were evaluated as specific findings for MSA. As the field strength increased, the occurrence of hyperintensity both at the dorsolateral outer putaminal margin and of the putaminal body decreased, while the occurrence of hypointensity at the dorsolateral putaminal margin increased in MSA. The occurrence of uniform mild hyperintensity of the outer putaminal margin was evident in 7% at 0.35T, 40% at 1.5T, and 47% at 3.0T in MSA and in 5% at 0.35T, 60% at 1.5T, and 75% at 3.0T in PD. However, no PD patients showed hyperintensity at the dorsolateral outer putaminal margin and that of the putaminal body. Putaminal magnetic resonance imaging (MRI) findings in MSA were altered considerably by magnetic field strength. The severity and distribution of signal changes are important for assessing putaminal MRI findings in MSA. © 2010 Movement Disorders Society     

Perverted head‐shaking and positional downbeat nystagmus in patients with multiple system atrophy

The diagnosis of multiple system atrophy (MSA) is mainly based on the clinical criteria, which are often of little assistance in the early stages of the disease. Positional downbeat nystagmus (pDBN) and perverted head‐shaking nystagmus (pHSN), possible signs of cerebellar dysfunction, may be useful in differentiating MSA from other parkinsonian disorders. To investigate the occurrences of pDBN and pHSN in patients with MSA compared with those in patients with Parkinson's disease (PD). A total of 127 consecutive patients with MSA and 274 patients with PD underwent a video‐oculographic recording of head‐shaking and positional nystagmus over a year. The occurrences of pDBN and pHSN were higher in MSA than in PD. pDBN was more frequently observed in MSA with overt cerebellar signs than in those without, but the occurrence of pHSN did not differ between the MSA groups. pHSN was more frequently observed in MSA‐p without overt cerebellar signs than in PD, but there was no difference in the occurrence of pDBN between them. The presence of pHSN and pDBN may be a clue for the diagnosis of MSA, and pHSN may be helpful in differentiating MSA‐p from PD when the patients do not have overt cerebellar features. © 2009 Movement Disorder Society     

Cognitive profiling in relation to short latency afferent inhibition of frontal cortex in multiple system atrophy

BackgroundCognitive dysfunction occurs in multiple system atrophy (MSA) more frequently than previously known. As a type of synucleinopathy, pathology spreads widely in cortical and subcortical areas as the disease advances. The exact anatomical and imaging substrates, and electrophysiological or biochemical indicators of cognitive impairment in MSA are not yet clear. Diminished short-latency afferent inhibition (SAI) of motor cortex was shown to be an electrophysiological correlate of dementia and mild cognitive impairment associated to Parkinson's disease (PD). We hypothesize that it can also be electrophysiological correlate of cognitive impairment in MSA.MethodsWe studied SAI and a neuropsychological test battery in 19 non-demented MSA patients (11 MSA-P and 8 MSA-C), 10 non-demented PD patients and 10 healthy controls. Neuropsychological test scores were grouped in four main cognitive domains (attention, memory, executive and visuo-spatial functions) and were analyzed by factor analysis.ResultsAll subject groups were matched for age. Moreover, the MSA-P, MSA-C, and PD groups were matched for disease duration. Scores of cognitive domains were similar in MSA and PD cases, while scores in attention, executive and visuo-spatial domains were worse in MSA than controls (p < 0.05). SAI was normal in PD but decreased in MSA patients by reaching statistical significance in MSA-C subtype. SAI response was correlated with cognitive performances measured by factor scores of neuropsychological test battery in all study subjects.ConclusionsThese results show that cognitive functions are impaired in MSA patients compared to controls as well as a parallel reduction in SAI response.     

Brain-derived neurotrophic factor gene polymorphisms in Japanese patients with sporadic Alzheimer's disease, Parkinson's disease, and multiple system atrophy.

We studied two genetic polymorphisms (240C/T and 480G/A) of the brain-derived neurotrophic factor (BDNF) gene in Japanese patients with Alzheimer's disease (AD, n = 172), Parkinson's disease (PD, n = 327), and multiple system atrophy (MSA, n = 122), as well as controls (n = 275). The distribution of the 240 C/T polymorphism was significantly different between AD patients and controls, whereas there was no difference in the genotype of the two polymorphisms between MSA and controls or between PD and controls. Our data suggest that BDNF might play a role in AD.     

Loss of substantia nigra hyperintensity on 7 Tesla MRI of Parkinson's disease,multiple system atrophy,and progressive supranuclear palsy

BackgroundSeven Tesla (7T) MRI can visualize anatomical alterations occurring in a hyperintense structure of the substantia nigra in Parkinson's disease (PD).ObjectiveWe investigated whether 7T MRI can detect the loss of substantia nigra hyperintensity in patients with PD, multiple system atrophy (MSA), and progressive supranuclear palsy (PSP).MethodsUsing 7T MRI, we evaluated 26 healthy subjects, 30 patients with PD, 7 patients with MSA, and 3 patients with PSP. Two blinded readers independently assessed the images. We carried out a comparative analysis of five patients with hemiparkinsonism via ¹²³I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane (¹²³I-FP-CIT) SPECT.Results7T MRI revealed a definitive shape of nigral hyperintensity in healthy subjects, nearly identical to neuropathological characterization of nigrosome 1, and enabled instantaneous determination of its presence or absence in all subjects. Nigral hyperintensity was lost in all patients with PD, MSA with predominant parkinsonism, and PSP. One of five patients with MSA with predominant cerebellar ataxia showed an intact nigral hyperintensity. The side effects were mild and tolerable, and imaging was successful in patients with dyskinesia. Motion artifact incidence was higher in elderly subjects. In hemiparkinsonism cases, we observed partial loss of nigral hyperintensity on the side of less reduced ¹²³I-FP-CIT binding, suggesting an ongoing iron deposition on the unaffected side in hemiparkinsonism.ConclusionsThe present findings suggest that 7T MRI represents an excellent tool for evaluating nigral hyperintensity in PD, MSA, and PSP, with tolerable side effects and limited motion artifacts. Thus, imaging of parkinsonism may benefit from using 7T MRI.     

Morphology and signal changes of the lentiform nucleus based on susceptibility weighted imaging in parkinsonism-predominant multiple system atrophy

IntroductionIt remains challenging to make a differential diagnosis between atypical parkinsonism and Parkinson's disease (PD) from routine neuroimaging. This case-control study aimed to quantitatively investigate both morphological and signal intensity changes in susceptibility weighted imaging (SWI) of the lentiform nucleus (LN) for discriminating parkinsonism-predominant multiple system atrophy (MSA-P) from PD.MethodsWe retrospectively enrolled patients with MSA-P, PD, and sex- and age-matched controls between January 2016 and November 2019 at the Movement Disorder Center who underwent 3T MR imaging of brain with SWI sequence. Two specialists at the center reviewed the medical records and made the final diagnosis, and two experienced neuroradiologists performed MRI image analysis based on a defined radiological protocol to conduct the ROI-based morphological measurements of the LN and the signal intensity.ResultsA total of 19 patients with MSA-P, 19 patients with PD and 19 controls were enrolled in this study. We found that patients with MSA-P had significant decreases size in the short line (SL) and the ratio of the SL and the long line (SLLr) and increased value in the signal intensity standard deviation of the LN (SIsd_LN) compared with the patients with PD and with the controls (P < 0.05). Combining these three indexes, this finding had a sensitivity of 94.7% and a specificity of 63.2% to distinguish MSA-P from PD.ConclusionAs compared to PD and control subjects, the SA-P patients are characterized by narrowing morphology and the inhomogeneous signal intensity of the posterior region of LN. The quantitative morphological change is a possible potential marker to differentiate MSA-P from PD on SWI.     

The phenomenon of disproportionate antecollis in Parkinson's disease and multiple system atrophy.

We sought to explore the phenomenon of disproportionate antecollis in multiple system atrophy (MSA) and Parkinson's disease (PD). The etiology is much debated and the main issue is whether it represents a primary myopathy or is secondary to the underlying motor disorder. The clinical, electrophysiological, and biopsy data of MSA or PD patients with antecollis were reviewed. We reviewed 16 patients (7 MSA and 9 PD) who developed antecollis during the course of their disease. The interval between onset of motor symptoms and of antecollis was shorter in the MSA group (4.6 +/- 1.7 years vs. 10.5 +/- 7.0 years). In 6 patients, the antecollis developed subacutely, and in 2 the abnormal neck flexion was initially an off-period phenomenon. Two additional patients also showed some dopa-responsiveness. Clinically, the antecollis was characterized by a forward flexion and anterior shift of the neck, with prominent cervical paraspinal and levator scapulae muscles, usually without weakness of residual neck extension. Electromyography of cervical paraspinal muscles showed mixed myopathic, normal, and neurogenic units, without early recruitment. Cervical paraspinal muscle biopsy in 2 patients disclosed fibrosis and nonspecific myopathic changes. We suggest that, in the context of MSA or PD, the initiating event in antecollis could be a disproportionately increased tone in anterior neck muscles that leads to secondary fibrotic and myopathic changes. However, a primary but yet unexplained neck extensor myopathy still remains the alternative possibility and longitudinal studies are necessary to settle this issue.