Progressive supranuclear palsy responding to intravenous thiamine: superimposed Wernicke's encephalopathy?

Progressive supranuclear palsy (PSP) may be a risk factor for thiamine deficiency. The classic symptoms of PSP (postural instability, supranuclear vertical gaze palsy and dementia) overlap with the clinical triad of Wernicke's encephalopathy (cognitive impairment, gait problems and ocular abnormality). Therefore, superimposed thiamine deficiency in patients with PSP may aggravate the pre-existing symptoms of PSP. Here, we are reporting a 64-year-old woman having supranuclear ocular palsy, gait instability and dementia for the past 2-3 years. The patient fulfilled the diagnostic criteria of PSP. In parallel, she fulfilled the Caine's criteria of Wernicke's encephalopathy. Her serum thiamine level was low. Supplementation of thiamine led to marked improvement in the symptoms which had been present for many years. These symptoms were originally presumed to be due to PSP. This case highlights the needs to identify superimposed thiamine deficiency in patients with PSP.

Intrinsic functional connectivity alterations in progressive supranuclear palsy: Differential effects in frontal cortex, motor, and midbrain networks.

BACKGROUND: The topography of functional network changes in progressive supranuclear palsy can be mapped by intrinsic functional connectivity MRI. The objective of this study was to study functional connectivity and its clinical and behavioral correlates in dedicated networks comprising the cognition-related default mode and the motor and midbrain functional networks in patients with PSP. METHODS: Whole-brain-based "resting-state" functional MRI and high-resolution T1-weighted magnetic resonance imaging data together with neuropsychological and video-oculographic data from 34 PSP patients (22 with Richardson subtype and 12 with parkinsonian subtype) and 35 matched healthy controls were subjected to network-based functional connectivity and voxel-based morphometry analysis. RESULTS: After correction for global patterns of brain atrophy, the group comparison between PSP patients and controls revealed significantly decreased functional connectivity (P < 0.05, corrected) in the prefrontal cortex, which was significantly correlated with cognitive performance (P = 0.006). Of note, midbrain network connectivity in PSP patients showed increased connectivity with the thalamus, on the one hand, whereas, on the other hand, lower functional connectivity within the midbrain was significantly correlated with vertical gaze impairment, as quantified by video-oculography (P = 0.004). PSP Richardson subtype showed significantly increased functional motor network connectivity with the medial prefrontal gyrus. CONCLUSIONS: PSP-associated neurodegeneration was attributed to both decreased and increased functional connectivity. Decreasing functional connectivity was associated with worse behavioral performance (ie, dementia severity and gaze palsy), whereas the pattern of increased functional connectivity may be a potential adaptive mechanism. © 2017 International Parkinson and Movement Disorder Society.

Aspiration pneumonia and bronchopneumonia in progressive supranuclear palsy treated with qing fei tang: two case reports.

INTRODUCTION: Qing fei tang, which is used for various respiratory diseases, is useful for reducing relapse of aspiration pneumonia and bronchopneumonia in stroke, but the effect remains unknown in Parkinson's syndrome. We report two cases of Japanese patients with progressive supranuclear palsy and relapsing aspiration pneumonia and bronchopneumonia, which was successfully prevented by qing fei tang. CASE PRESENTATION: Two Japanese men with progressive supranuclear palsy and receiving total enteral feeding (patient one (66-years-old) and patient two (76-years-old)) had experienced recurrent aspiration pneumonia and bronchopneumonia, which was unresponsive to conventional therapy. The respiratory infection developed twice at intervals of two months in patient one, and nine times at almost monthly intervals in patient two. Thereafter, they were given qing fei tang. After administration of qing fei tang, the respiratory infection reoccurred only once; after 5.5 months for patient one, and six months for patient two. Both of our patients clearly showed a reduced incidence of respiratory infection. CONCLUSIONS: Both of our patients clearly showed a reduced incidence of respiratory infection after the administration of qing fei tang. Qing fei tang could be useful for the prevention of recurrent aspiration pneumonia and bronchopneumonia in progressive supranuclear palsy.

Brainstem and spinal reflex studies in patients with primary progressive freezing of gait.

Our aim was to investigate the extent and pattern of involved pathways using brainstem and spinal reflexes by comparing primary progressive freezing of gait (PPFOG) progressive supranuclear palsy (PSP) with FOG. Seven patients with PPFOG and age and sex matched seven PSP patients and 16 healthy subjects were included in the study. All subjects underwent blink reflex (BR), trigemino-cervical reflex (TCR), auditory startle reflex (ASR) and long latency flexor reflex (LLFR) investigations under the same conditions. All three groups had normal BR latencies. ASR probability was lowest in the PSP group and was highest in PPFOG (p=0.005). The presence rate of TCR was lowest in PSP and it was highest in PPFOG (p=0.007 for SC and p=0.023 for SCM). The presence rate and amplitude of LLFR (R II) were decreased in the PSP group (p=0.010 and p=0.031, respectively) whereas it was in a continuous pattern in some of PPFOG patients. ASR, TCR and LLFR were all inhibited in PSP and we suggest that suppression of all three reflexes is probably related to degeneration of brainstem reticular formation and basal ganglia connections. However, interestingly, in PPFOG, excitabilities of ASR and TCR circuits are increased suggesting loss of pathways mediating suprasegmental control.

Fluorodeoxyglucose positron emission tomography in Richardson's syndrome and progressive supranuclear palsy-parkinsonism.

BACKGROUND: We hypothesized that postural instability and cognitive decline in patients with Richardson's syndrome could be a consequence of reduced thalamic and frontal metabolism. Severe Parkinsonian signs in patients with progressive supranuclear palsy-parkinsonism may be reflected by alterations in putaminal metabolism. METHODS: Eleven patients with Richardson's syndrome, 8 patients with progressive supranuclear palsy-parkinsonism, 12 with Parkinson's disease, and 10 controls underwent clinical assessment and fluorodeoxyglucose positron emission tomography (PET). RESULTS: Richardson's syndrome patients showed pronounced thalamic hypometabolism, and patients with progressive supranuclear palsy-parkinsonism pronounced putaminal hypometabolism, compared to all other investigated groups. The putamen/thalamus uptake ratio differentiated progressive supranuclear palsy-parkinsonism from Richardson's syndrome (area under the curve 5 0.86) and from Parkinson's disease (area under the curve 5 0.80) with acceptable accuracy. Frontal hypometabolism was predominantly found in Richardson's syndrome patients. CONCLUSIONS: Richardson's syndrome, progressive supranuclear palsy-parkinsonism and Parkinson's disease showed different metabolic patterns in fluorodeoxyglucose PET.

Obsessive-compulsive behavior as a symptom of dementia in progressive supranuclear palsy.

AIMS: To describe obsessive-compulsive symptoms (OCS) as under-recognized behavioral and psychological symptoms of dementia of progressive supranuclear palsy (PSP) and to discuss possible mechanisms based on MRI and SPECT findings. METHODS: We studied 74 PSP patients. OCS are defined as persistent and unreasonable, but non-delusional/hallucinatory, ideas and behaviors. Demography, cognition, the widths of middle cerebellar peduncles (MCP) and the inter-caudate distances (ICD), both corrected by the intracranial size (MCP and ICD ratios), and changes on voxel-based SPECT were compared between the subgroups with and without OCS. Finally, the predicative power of various factors to OCS was investigated. RESULTS: We observed OCS in 18 patients (24%). They were obsessed with daily trifles and physical symptoms among other things. OCS was not associated with demography or cognitive levels. OCS-positive patients had significantly smaller MCP and ICD ratios and showed marked uptake decreases in the orbitofrontal cortex, caudate and thalamus. Relative uptake increases in the cerebellum, specifically the tonsils, were milder in OCS-positive than -negative patients. A smaller right MCP, a smaller ICD ratio and lower uptake increases in the right cerebellar were the significant predictors of OCS. CONCLUSIONS: OCS are frequent but under-recognized behavioral and psychological symptoms of dementia in PSP. Dysfunction of the fronto-caudate-thalamus-cerebellum circuit may be involved.

Sound naming in neurodegenerative disease.

Modern cognitive neuroscientific theories and empirical evidence suggest that brain structures involved in movement may be related to action-related semantic knowledge. To test this hypothesis, we examined the naming of environmental sounds in patients with corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP), two neurodegenerative diseases associated with cognitive and motor deficits. Subjects were presented with 56 environmental sounds: 28 sounds were of objects that required manipulation when producing the sound, and 28 sounds were of objects that required no manipulation. Subjects were asked to provide the name of the object that produced the sound and also complete a sound-picture matching condition. Subjects included 33 individuals from four groups: CBD/PSP, Alzheimer disease, frontotemporal dementia, and normal controls. We hypothesized that CBD/PSP patients would exhibit impaired naming performance compared with controls, but the impairment would be most apparent when naming sounds associated with actions. We also explored neural correlates of naming environmental sounds using voxel-based morphometry (VBM) of brain MRI. As expected, CBD/PSP patients scored lower on environmental sounds naming (p<0.007) compared with the controls. In particular, the CBD/PSP patients scored the lowest when naming sounds of manipulable objects (p<0.05), but did not show deficits in naming sounds of non-manipulable objects. VBM analysis across all groups showed that performance in naming sounds of manipulable objects correlated with atrophy in the left pre-motor region, extending from area six to the middle and superior frontal gyrus. These results indicate an association between impairment in the retrieval of action-related names and the motor system, and suggest that difficulty in naming manipulable sounds may be related to atrophy in the pre-motor cortex. Our results support the hypothesis that retrieval of action-related semantic knowledge involves motor regions in the brain.

Balance and eye movement training to improve gait in people with progressive supranuclear palsy: quasi-randomized clinical trial.

BACKGROUND AND PURPOSE: Although vertical gaze palsy and gait instability are cardinal features of progressive supranuclear palsy (PSP), little research has been done to address oculomotor and gait rehabilitation for PSP. The purpose of this study was to compare the benefits of a program of balance training complemented with eye movement and visual awareness training versus balance training alone to rehabilitate gait in people with PSP. PARTICIPANTS: Nineteen people moderately affected by the disease were assigned to either a treatment group (balance plus eye movement exercises, n=10) or a comparison group (balance exercises only, n=9) in a quasi-random fashion. METHODS: The baseline characteristics assessed were diagnosis (possible versus probable), sex, age, time of symptom onset, dementia, and severity of symptoms. Within-group, between-group, and effect size analyses were performed on kinematic gait parameters (stance time, swing time, and step length) and clinical tests (8-ft [2.4-m] walk test and Timed "Up & Go" Test). RESULTS: The within-group analysis revealed significant improvements in stance time and walking speed for the treatment group, whereas the comparison group showed improvements in step length only. Moderate to large effects of the intervention were observed for the treatment group, and small effects were observed for the comparison group. The between-group analysis did not reveal significant changes for either group. DISCUSSION AND CONCLUSION: These preliminary findings support the use of eye movement exercises as a complementary therapy for balance training in the rehabilitation of gait in people with PSP and moderate impairments. Additional studies powered at a higher level are needed to confirm these results.

Functional mapping in PD and PSP for sustained phonation and phoneme tasks.

AIM: To elucidate the central basis of articulatory speech disorders in Parkinsonian syndromes using functional magnetic resonance imaging (fMRI). METHODS: Twenty-two patients with Parkinson's disease (PD) and 18 with progressive supranuclear palsy (PSP) were clinically evaluated for speech dysfunction. Functional magnetic resonance imaging (fMRI) was carried out in these patients using sustained phonation and phoneme tasks. Individual and group analysis using SPM2 was done for eight patients with PD, 7 with PSP and 6 healthy controls. SETTING: Tertiary Medical Teaching Institute. RESULTS: For sustained phonation paradigm, superior temporal gyrus area was activated in PD patients, and occipital cortex in PSP subjects in comparison to controls. For phoneme paradigm, the patients with PD recruit lingual gyrus obviating the need for more efforts for the task. Also wider areas as well as more clusters were activated in PD patients compared to controls. Lingual gyrus was found to be strongly activated in PSP patients. Reduced activation of the primary areas with recruitment of remote areas was another prominent finding in PSP. Due to excessive motion (>1.5 mm, >1 degrees ) in all the MSA patients, they could not be considered for analysis. CONCLUSION: The failure of the executive fronto-striatal network would lead to increased activation of other areas in PD, but in PSP, there is a widespread cortical dysfunction.

Attention and cognition in bradykinetic-rigid syndromes: an event-related potential study.

Bradykinetic-rigid syndromes are often accompanied by cognitive impairment. Because prominent motor involvement in these disorders may interfere with neuropsychological testing, we used event-related potentials (ERPs) for the assessment of cognition and attention in 41 patients with various bradykinetic-rigid syndromes of less than 5 years duration: idiopathic Parkinson's disease corticobasal degeneration, Steele-Richardson-Olszewski syndrome (SRO), and multiple system atrophy. Patients were compared with matched normals. ERP abnormalities in the auditory "oddball" paradigm were found only in corticobasal degeneration and SRO. ERP abnormalities in selective attention tasks were present in all patient groups, changes in SRO being the most prevalent. Abnormalities in corticobasal degeneration were present under "less-attention-demanding" conditions and suggested involvement of posterior parts of the brain. Multiple system atrophy and idiopathic Parkinson's disease patient groups had minimal ERP abnormalities. However, reaction times in MSA were longer in all paradigms. The results of the study support the view that bradykinetic-rigid syndromes involve some attentional deficits, but also have distinct reaction time and ERP characteristics, which may be helpful in differential diagnosis.

[The thalamic changes in progressive supranuclear palsy].

This report is to investigate neuropathological changes of the thalamus observed in progressive supranuclear palsy. Six autopsy cases were examined. They were 5 males and a female, whose age was between 57 and 72 years old. They developed dementia in various degrees and three of the cases showed periodic stuporous state and akinetic mutism in the last stage. The paraffined thin-sections were stained with hematoxylin-eosin, luxol-fast-blue, Holzer, modified Bielschowsky, Gallyas and anti-tau stainings. The histological changes were evaluated in the aspects of neuronal loss, fibrillary gliosis and neurofibrillary tangles. In conclusion, there were three types in six cases. The first was seen in two cases and that there appeared many Alzheimer's neurofibrillary tangles (NFTs) in medial nuclei, lateral and ventral nuclei as well as zona incerta and reticular nucleus. The second was observed in two cases and that the loss of nerve cells was severe, especially in medial nuclei and the dorsal part of lateral and ventral nuclei and fibrillary gliosis was observed beyond the lesions of neuronal loss. The third was that the appearance of NFTs was moderate in number and neuronal loss was minimal. Moreover, neuronal loss and NFTs of zona incerta were common in these cases. Argentophilic fibrillary inclusions were observed in the neuropil and astrocytes in all cases. It is important to investigate the correlations between neuropathological changes and clinical manifestations, especially in the peculiar type of dementia observed in PSP. The thalamic changes of PSP may play an important role in causing stuporous state and akinetic mutism as well as subcortical dementia.