The Enigma That is Rectal Squamous Cell Carcinoma: A Case Series.

INTRODUCTION: Colorectal cancer is the third most common cancer and the third leading cause of cancer deaths in the United States. As rectal squamous cell carcinoma (SCC) is an uncommon colorectal cancer, there is limited data on this clinical entity. We aimed to evaluate the tumor characteristics, treatment, and clinical outcomes of this rare deadly disease. METHODS: Pathological specimens from 2017 to 2022 at a single National Cancer Institute-designated cancer center were screened for all rectal cases with a diagnosis of SCC. All patients with a primary rectal SCC were included. Patients who had extension to the dentate line or evidence of an anal mass, and those who were treated at an outside institution, were excluded. Demographic, treatment, outcome, and surveillance data was extracted. RESULTS: There were 56 specimens identified, nine of which met inclusion criteria. Most patients were White (78%), Hispanic (78%), and female (67%). The average age at diagnosis was 57 y [52-65]. All patients had nodal involvement at the time of clinical staging. All patients were treated with Nigro protocol, with one patient treated with surgery first. The median time of follow-up was 12 mo after initial treatment, 33% had recurrence, with median time to recurrence of 25 mo. Overall, mortality from rectal SCC was 33% at a median time of 37 mo from initial diagnosis. CONCLUSIONS: Rectal SCC is a colorectal cancer that is not fully understood. Our findings showed that treatment mirrors that of anal SCC, with similar rates of survival to both rectal adenocarcinoma and anal SCC.

Relationship between anal cancer recurrence and cigarette smoking.

BACKGROUND: The incidence of anal cancer has been increasing in the United States. Smoking is a well-established risk factor; however, the impact of smoking on disease re-currence and outcome has not been well studied. The aim of this study was to assess the association between anal cancer recurrence and cigarette smoking. AIM: To investigate the relationship between cigarette smoking status and anal cancer treatment outcome. METHODS: The cancer registry from a single, community hospital was screened for patients with anal cancer between 2010 and 2021. The following characteristics were gathered from the database: Age; sex; cigarette smoking history; American Joint Committee on Cancer Clinical Stage Group; response to therapy; recurrence; time to recurrence; mortality; time to death; and length of follow-up. Patients were divided into the following groups: Current smokers; former smokers; and never smokers. SPSSv25.0 software (IBM Corp., Armonk, NY, United States) was used for statistical analysis. RESULTS: A total of 95 patients from the database met the screening criteria. There were 37 never smokers, 22 former smokers, and 36 current smokers. There was no difference between groups in regards to race or sex. There was no difference in the American Joint Committee on Cancer Clinical Stage Group between groups. The former smokers were significantly older when compared to never smokers and current smokers (66.5 ± 13.17 vs 57.4 ± 7.82 vs 63.7 ± 13.80, P = 0.011). Former smokers and current smokers had a higher recurrence rate compared to never smokers (30.8% and 20.8% compared to zero, P = 0.009). There was not a significant difference in recurrence between former smokers and current smokers. There was no difference in the mortality, non-response rate, or time to death between the groups. CONCLUSION: Our data contributes evidence that cigarette smoking status is associated with increased recurrence for patients with anal cancer.

Accelerated atrophy in dopaminergic targets and medial temporo-parietal regions precedes the onset of delusions in patients with Alzheimer's disease.

People with Alzheimer's disease (AD) and delusions have worse quality of life and prognosis. However, early markers of delusions have not been identified yet. The present study investigated whether there are any detectable differences in grey matter (GM) volume and cognitive changes in the year before symptom onset between patients with AD who did and did not develop delusions. Two matched samples of AD patients, 63 who did (PT-D) and 63 who did not develop delusions (PT-ND) over 1 year, were identified from the Alzheimer's Disease Neuroimaging Initiative database. The Neuropsychiatric Inventory (NPI) was used to assess the presence of delusions. Sixty-three additional matched healthy controls (HC) were selected. Repeated-measures ANCOVA models were used to investigate group-by-time effects on the volume of selected GM regions of interest and on cognitive performance. No neurocognitive differences were observed between patient groups prior to symptom onset. Greater episodic memory decline and GM loss in bilateral caudate nuclei, medio-temporal and midline cingulo-parietal regions were found in the PT-D compared with the PT-ND group. A pattern of faster GM loss in brain areas typically affected by AD and in cortical and subcortical targets of dopaminergic pathways, paralleled by worsening of episodic memory and behavioural symptoms, may explain the emergence of delusions in patients with AD.

A Rare Case of Rectal Squamous Cell Carcinoma Treated with Nigro Protocol.

Squamous cell carcinoma (SCC) of the rectum is a rare malignancy, and the optimal treatment strategy remains unknown. Cases are limited in the literature, and although historically treated with surgical resection, more recent cases have suggested success with chemotherapy. Although Nigro protocol was initially developed for anal SCC, we present a case of rectal SCC successfully treated with the Nigro protocol. Our case supports the use of chemoradiotherapy as initial treatment for rectal SCC over surgery.

An autopsy case of progressive supranuclear palsy. Pallido-nigro-luysian type with argyrophilic grains clinically presenting with personality and behavioral changes.

Pallido-nigro-luysian atrophy (PNLA) is a variant of progressive supranuclear palsy (PSP). Patients with PSP sometimes show psychiatric signs, but there are few reports about such signs being associated with PSP-PNLA. Here, we report a case of PSP-PNLA with argyrophilic grains (AGs) in a patient clinically diagnosed as having PSP-frontotemporal dementia (PSP-F). A 74-year-old man described as "kind" presented with impaired memory, irritability, and apathy. He showed levodopa-resistant parkinsonism and postural instability. Brain magnetic resonance imaging revealed mild atrophy of the midbrain and right-side-dominant atrophy of the hippocampus and temporal lobe. The patient was diagnosed as having PSP with frontal lobe cognitive or behavioral presentations (PSP-F). He died of aspiration pneumonia at age 81. At autopsy, macroscopic examination revealed depigmentation of the substantia nigra and grayish discoloration of the dentate nucleus, globus pallidus, and subthalamic nucleus. Severe gliosis was observed in the same regions. There were many phosphorylated tau-immunoreactive equivocal tufted astrocytes in the globus pallidus. Many neurofibrillary tangles and neuropil threads were observed in the substantia nigra and subthalamic nucleus, and few tau aggregates were observed in the frontal cortex. In contrast, AGs were abundant in the amygdala, entorhinal cortex, and anterior cingulate gyrus, with an asymmetric distribution. The pathological observations led us to change the diagnosis to PSP-PNLA with AGs. Although most cases of PSP-F derive from tau pathology in the frontal cortex, this patient did not have phosphorylated tau-immunoreactive aggregates in that location. Our observations suggest that the psychiatric signs of PSP-F should be considered as being due to the presence of limbic AGs, not frontal tau pathology.

Pathogenic LRRK2 control of primary cilia and Hedgehog signaling in neurons and astrocytes of mouse brain.

Activating LRRK2 mutations cause Parkinson's disease, and pathogenic LRRK2 kinase interferes with ciliogenesis. Previously, we showed that cholinergic interneurons of the dorsal striatum lose their cilia in R1441C LRRK2 mutant mice (Dhekne et al., 2018). Here, we show that cilia loss is seen as early as 10 weeks of age in these mice and also in two other mouse strains carrying the most common human G2019S LRRK2 mutation. Loss of the PPM1H phosphatase that is specific for LRRK2-phosphorylated Rab GTPases yields the same cilia loss phenotype seen in mice expressing pathogenic LRRK2 kinase, strongly supporting a connection between Rab GTPase phosphorylation and cilia loss. Moreover, astrocytes throughout the striatum show a ciliation defect in all LRRK2 and PPM1H mutant models examined. Hedgehog signaling requires cilia, and loss of cilia in LRRK2 mutant rodents correlates with dysregulation of Hedgehog signaling as monitored by in situ hybridization of Gli1 and Gdnf transcripts. Dopaminergic neurons of the substantia nigra secrete a Hedgehog signal that is sensed in the striatum to trigger neuroprotection; our data support a model in which LRRK2 and PPM1H mutant mice show altered responses to critical Hedgehog signals in the nigrostriatal pathway.

Dream Enactment Behavior Disorder Associated with Pallido-Nigro-Luysian Degeneration and Tau Proteinopathy.

BACKGROUND: Pallido-nigro-luysian atrophy (PNLA) is a rare neurodegenerative disorder with only a few cases reported to date. Although the clinical picture usually resembles progressive supranuclear palsy, pathological examination reveals more selective atrophy and loss of neurons in the globus pallidus, substantia nigra and subthalamic nucleus. OBJECTIVES: To describe the clinical features and pathological findings of a patient with PNLA. METHODS: Case report with clinico-pathological discussion. RESULTS: An 83-year-old man presented to our clinic with a vertical supranuclear gaze palsy, parkinsonism, gait impairment and sleep abnormalities suggestive of REM-sleep behavior disorder. Neuropathological examination 5 years after symptom onset revealed subcortical tau proteinopathy compatible with a PNLA pattern. There was also an associated mild degree of limbic/subcortical inflammatory response, Alzheimer's disease-related changes, as well as argyrophilic grain disease. CONCLUSIONS: We present a comprehensive clinico-pathological discussion of a patient with PNLA. Besides parkinsonism and vertical supranuclear gaze palsy, the patient also had a sleep disorder, clinically suggestive of REM behavioral disorder, which has not been previously reported in PNLA. We expand the clinical phenotype of this rare condition and provide neuropathological evidence for the associated abnormalities.

Evolution of the Role of Radiotherapy for Anal Cancer.

Prior to the 1980s, the primary management of localized anal cancer was surgical resection. Dr. Norman Nigro and colleagues introduced neoadjuvant chemoradiotherapy prior to abdominoperineal resection. Chemoradiotherapy 5-fluorouracil and mitomycin C afforded patients complete pathologic response and obviated the need for upfront surgery. More recent studies have attempted to alter or exclude chemotherapy used in the Nigro regimen to mitigate toxicity, often with worse outcomes. Reductions in acute adverse effects have been associated with marked advancements in radiotherapy delivery using intensity-modulated radiation therapy (IMRT) and image-guidance radiation delivery, resulting in increased tolerance to greater radiation doses. Ongoing trials are attempting to improve IMRT-based treatment of locally advanced disease with efforts to increase personalized treatment. Studies are also examining the role of newer treatment modalities such as proton therapy in treating anal cancer. Here we review the evolution of radiotherapy for anal cancer and describe recent advances. We also elaborate on radiotherapy's role in locally persistent or recurrent anal cancer.

Neuropsychological spectrum in early PD: Insights from controlled and automatic behavioural regulation.

Initial changes in Parkinson's disease (PD) are marked by loss of automatic movements and decline of some cognitive functions. Yet, the exact profile and extent of cognitive impairments in early stages of PD as well as their mechanisms related to automatic motor dysfunction remain unclear. Our objective was to examine the neuropsychological changes in early PD and their association to automatic and controlled modes of behavioural control. Significant relationships between early PD and cognitive dysfunction in set-shifting, abstraction ability/concept formation, processing speed, visuospatial/constructional abilities and verbal-visual memory was found. We also noted that tests with a strong effortful and controlled component were similarly affected as automatic tests by early PD, particularly those testing verbal memory, processing speed and visuospatial/constructional functions. Our findings indicate that initial stages of PD sets constraints over most of the cognitive domains normally assessed and are not easily explained in terms of either automatic or controlled mechanisms, as both appear similarly altered in early PD.

Complicated Surgical Removal of an Adherent Port-a-Cath After 11 Years of Implantation.

A 65-year-old woman with a medical history significant for anal cancer was referred by her primary care physician for a port-a-cath removal. The port was placed prior to treatment of squamous cell carcinoma of the anus, 11 years prior to this scheduled removal. She received chemotherapy and radiation in accordance with the Nigro protocol, treating the anal cancer to complete resolution. During port removal, a fibrous capsule was dissected and the port was removed from the left upper breast border along with proximal portion of the catheter. Significant difficulty was found in removing the remaining catheter despite sustained traction and guidewire insertion. Fluoroscopy revealed an intravascular adhesion of the catheter tip in the superior vena cava, which could not be freed. In order to prevent vascular injury, the adhesed portion of the distal catheter was left in place with three large surgical clips placed distally. This case highlights the very rare complication of complete vascular adherence of the terminal catheter tip and extended port intracorporeal time as a risk factor for adhesion. This case also highlights the importance of timely permanent central venous catheter removal following completion of its intended regimen.

Anal canal squamous cell cancer: surgical therapy, when?

Aim To describe a therapeutic approach, indications for abdominoperineal resection (APR), survival and oncological results for patients who received treatment in our surgical clinic for anal canal squamous cell cancer (SCC). Methods Patients were randomized into two groups according to the treatment method: Group 1- Chemoradiotherapy (CRT) without surgery, Group 2- CRT + APR. Results Eighteen patients with anal canal SCC were included in the study; 11 (61.1%) patients were in Group 1 and 7 (38.8%) in Group 2. Reasons for APR was as follows: three patients had insufficient CRT, two had recurrence after CRT, one had complete faecal incontinence and one patient had rectovaginal fistula. Overall five year survival (OS) and disease free survival (DFS) was 77.7% and 72.7%, respectively. Comparing two groups five year OS was 90.9% and 57.1%, whereas DFS was 81.8%, 57.1%, respectively (p=0.389 and 0.324, respectively). Conclusion Gold standard therapy for anal canal SCC is CRT. However, APR should be applied as an escape treatment for patients suffering from tumour progression, insufficient CRT and recurrence (30%).

Reduced Frequency of Ipsilateral Express Saccades in Cervical Dystonia: Probing the Nigro-Tectal Pathway.

Background: Cervical dystonia is a hyperkinetic movement disorder of unknown cause. Symptoms of cervical dystonia have been induced in animals in which the integrity of the nigro-tectal pathway is disrupted, resulting in reduced inhibition of the deep layers of the superior colliculus. This same pathway is believed to play a critical role in saccade generation, particularly visually guided, express saccades. It was hypothesized that individuals with cervical dystonia would present with a higher frequency of express saccades and more directional errors. Methods: Eight individuals with cervical dystonia and 11 age- and sex-matched control participants performed three saccadic paradigms: pro-saccade, gap, and anti-saccade (120 trials per task). Eye movements were recorded using electro-oculography. Results: Mean saccadic reaction times were slower in the cervical dystonia group (only statistically significant in the anti-saccade task, F(1, 35)  =  4.76, p  =  0.036); participants with cervical dystonia produced fewer directional errors (mean 14% vs. 22%) in the anti-saccade task; and had similar frequencies of express saccades in the gap task relative to our control population (chi-square  =  1.13, p  =  0.287). All cervical dystonia participants had lower frequencies of express saccades ipsilateral to their dystonic side (the side to which their head turns), (chi-square  =  3.57, p  =  0.059). Discussion: The finding of slower saccadic reaction times in cervical dystonia does not support the concept of reduced inhibition in the nigro-tectal pathway. Further research is required to confirm the observed relationship between the lateralization of lower frequencies of express saccades and direction of head rotation in cervical dystonia.

Squamous cell carcinoma of the anal canal.

Anal squamous cell carcinoma (SCC) is a rare cancer and accounts for approximately 4% of all cancers of the lower alimentary tract. The dominant etiology is infection with human papilloma virus (HPV), which is the most common sexually transmitted disease in the United States. Integration of HPV DNA into the host genome seems to be the driving mechanism behind carcinogenesis. Vaccines directed against oncogenic HPV serotypes exist, and their utility for preventing anal neoplasia is under investigation. Additional risk factors for developing SCC include HIV infection, anal receptive intercourse, smoking, and immunosuppression. Patients with known anal intraepithelial neoplasia (AIN) must be carefully screened with periodic digital rectal exam and anoscopy. The most common presenting symptom is bleeding, with up to one third of patients presenting asymptomatic. Once tissue diagnosis is made, staging of primary tumor is accomplished with either MRI or transanal ultrasound. Distant disease is evaluated with CT of chest abdomen and pelvis vs whole body PET/CT. The gold standard treatment for stage I-III disease remains the Nigro protocol, first described in 1974. Stage I disease not involving sphincter may be treated with local excision. Distant disease is treated with systemic chemotherapy with radiation reserved for locoregional symptoms. Careful surveillance is mandatory after completion of chemoradiation. Salvage abdominoperineal resection can achieve locoregional control in up to 77% of patients with persistent or recurrent disease. Morbidity is high, mostly owing to wound complications, and as such a flap reconstruction of the perineum is warranted.

Nigrostriatal dopamine transporter availability in early Parkinson's disease.

BACKGROUND: The imaging of biomarkers for characterization of dopaminergic impairment in Parkinson's disease (PD) is useful for diagnosis, patient stratification, and assessment of treatment outcomes. [18 F]FE-PE2I is an improved imaging tool allowing for detailed mapping of the dopamine transporter protein in the nigro-striatal system at the level of cell bodies (substantia nigra), axons, and presynaptic terminals (striatum). OBJECTIVES: The objective of this study was to compare the dopamine transporter protein loss in the presynaptic terminals to that in the cell bodies and axons in early PD patients using [18 F](E)-N-(3-iodoprop-2-enyl)-2b-carbofluoroethoxy-3b-(4'-methyl-phenyl) nortropane ([18 F]FE-PE2I) and high-resolution PET. METHODS: A total of 20 early PD patients (15 men/5 women, 62 ± 8 years) and 20 controls (15 men/5 women, 62 ± 7 years) underwent high-resolution [18 F]FE-PE2I PET. Dopamine transporter protein availability was estimated for the different nigro-striatal regions and expressed as nondisplaceable binding potential values. RESULTS: When compared with controls, the binding potential values in PD patients were reduced by 36% to 70% in presynaptic terminals and by 30% in cell bodies. Dopamine transporter availability along the tracts was not different between the 2 groups (controls 0.5 ± 0.1 vs PD 0.4 ± 0.1). CONCLUSIONS: This is the first study that examines dopamine transporter protein availability in vivo within the entire nigro-striatal pathway. The results suggest that at early stages of symptomatic PD a greater loss is observed at the level of the axonal terminals when compared with cell bodies and axons of dopaminergic neurons. The findings suggest a relative preservation of cell bodies in early PD, which might be relevant for novel disease-modifying strategies. © 2018 International Parkinson and Movement Disorder Society.

Ifngr1 and Stat1 mediated canonical Ifn-γ signaling drives nigrostriatal degeneration.

Brain expression of AAV-Ifn-γ leads to reactive gliosis, nigrostriatal degeneration and midbrain calcification in wild type mice. This mouse model phenocopies idiopathic basal ganglia calcification which is associated with Parkinsonian symptoms. To understand how the nigro-striatal pathway is selectively vulnerable to Ifn-γ, we determined if the phenotype is driven by canonical signaling intermediates, Ifngr1 and Stat1. Using focused bioinformatic analysis and rotarod testing, we show that neuroinflammation and motor abnormalities precede the appearance of midbrain neuropathologies in the brains of Ifn-γ mouse model. To test whether canonical Ifn-γ signaling is a key driver of progressive nigrostriatal degeneration, we overexpressed Ifn-γ in the brains of Ifngr1-/- and Stat1-/- mice. Expression of Ifn-γ in Ifngr1-/- mice did not result in any neuroinflammation, midbrain calcinosis or nigrostriatal degenerative pathology. Interestingly, in Stat1-/- mice, Ifn-γ expression resulted in gliosis without recapitulating the neurodegenerative phenotype. Overall, our data shows that canonical Ifn-γ signaling triggers midbrain calcinosis and nigrostriatal neurodegeneration, providing mechanistic insights into cytokine-driven selective neuronal vulnerability. Our study establishes the broader relevance of inflammatory signaling in neurodegenerative diseases and can potentially identify novel immunological targets for Parkinsonian syndromes.

Anal canal squamous cell cancer: are surgical alternatives to chemoradiation just as effective?

PURPOSE: The purpose of this paper is to study long-term oncologic outcomes after different treatment strategies for anal canal cancer (SCAC). METHODS: Patients with SCAC (2004-2013) were identified from Surveillance, Epidemiology, and End Results (SEER) database. Patients undergoing radiation (RT) were compared to those undergoing local excision (LE), abdominoperineal resection (APR), and abdominoperineal resection after radiation (RT + APR). Overall survival (OS) and cancer-specific survival (CSS) data were evaluated using Kaplan-Meier and Cox regression. RESULTS: Two thousand seven hundred and seventy-two (83.8%) patients underwent RT, 382 (11.6%) LE, 77 (2.3%) APR, 76 (2.3%) RT + APR. Median age for the four groups was 60, 57, 64, and 56 years and 32, 49.7, 53.2, and 39.5% were male, respectively, while median tumor size was 4.4, 2.6, 5.3, and 5.5 cm, respectively. Five-year OS of RT, LE, APR, and RT + APR groups was 63.7, 79.6, 25.8, and 41.8% while CSS was 79.6, 92.5, 75.6, and 58.8%, respectively, (p < 0.001). Adjusted hazard ratios for OS for LE, APR, and RT + APR with RT as reference were 1.007 (0.702-1.444), 2.311 (1.367-3.906), and 2.072 (1.016-4.228), respectively. CONCLUSION: These data suggest that APR does not provide better outcomes in treatment of SCAC. Chemoradiation remains the gold standard treatment for majority of patients. Local excision is associated with favorable outcomes in some circumstances.

Pathological and immunoblot analysis of phosphorylated TDP-43 in sporadic amyotrophic lateral sclerosis with pallido-nigro-luysian degeneration.

Transactivation response DNA-binding protein 43 kDa (TDP-43) is a key protein of sporadic amyotrophic lateral sclerosis (ALS), and phosphorylated form of TDP-43 (p-TDP-43) is a major pathological protein that accumulates in sporadic ALS. p-TDP-43 is found not only in primary motor neurons, but often propagates to non-motor systems as well. However, pallido-nigro-luysian (PNL) degeneration (PNLD) is rarely associated with ALS. We describe here a 68-year-old ALS patient presenting severe PNLD. He had difficulty walking due to poor movement of his right leg, and was diagnosed as having Parkinson's disease because of akinesia. About 2 years after onset, weakness of his left hand and leg led to a diagnosis of ALS. Tube feeding and non-invasive positive-pressure ventilation were initiated. He died of respiratory failure at the age of 71. There was no family history of either neurological disorders or dementia. Neuropathological examination revealed severe loss of neurons and gliosis in the PNL system in addition to the upper and lower motor neuron system. p-TDP-43 pathology was widespread in the PNL and motor neuron systems and also in the amygdala and hippocampus where no significant gliosis or neuronal loss was detected. Synuclein pathology was not observed in the investigated areas. Immunoblot analysis of p-TDP-43 C-terminal fragments showed a type B band pattern consistent with sporadic ALS. This is the first case of ALS with PNLD, in which p-TDP-43 distribution was widespread in the hippocampal formation (Nishihira type 2 and Brettschneider stage 4), and the type B immunoblot pattern was confirmed. Our case indicated that the PNL system can be involved in the disease process in sporadic ALS cases, although rarely. We also reviewed previous autopsy cases of ALS with PNLD to clarify the clinicopathological features.

Long-standing Crohn's disease and its implication on anal squamous cell cancer management.

BACKGROUND: Anal squamous cell carcinoma (ASCC) is rare, accounting for only 1% of gastrointestinal malignancies. We sought to better understand management strategies for ASCC in the setting of Crohn's disease (CD). METHODS: A retrospective chart review from 2001 to 2016 was conducted using ICD-9/10 codes for CD (555.9/K50) and ASCC (154.3/C44.520). Adult patients with a diagnosis of CD at the time of ASCC diagnosis were included. RESULTS: Seven patients (five female) were included with a median age of 50 years. The majority presented with perianal pain (three) and bleeding (four). Mean duration of CD was 20 years. Five patients had active perianal fistulizing disease at the time of ASCC diagnosis. Clinical stage at diagnosis of ASCC was stage 0 (n = 1), stage I (n = 1), stage II (n = 1), stage III (n = 2), stage IV (n = 1), and unknown (n = 1). All patients were treated with radiation and chemotherapy. Three patients experienced complications during radiation therapy: fistulizing disease, stenotic disease, and flap necrosis. Two patients had persistent disease at 6 months; one patient underwent abdominoperineal resection (APR) and the other chemotherapy and radiation. Two patients developed locally residual and metastatic disease and died within 1 year of diagnosis. Five-year disease-free survival was 56%. CONCLUSIONS: While the standard Nigro protocol remains standard of care in patients with ASCC, in the setting of CD, patients may be best approached as a case-by-case basis and may even require an operation first due to complications from radiation and aggressive nature of disease. Due to poor treatment outcomes, surveillance guidelines for this patient population are necessary.

123I-FP-CIT SPECT findings and its clinical relevance in prodromal dementia with Lewy bodies.

PURPOSE: Evidence for the prodromal stage of dementia with Lewy bodies (DLB) is very limited. To address this issue, we investigate the 123I-FP-CIT SPECT measure of dopamine transporter binding finding and its clinical relevance. METHODS: We enrolled subjects into a prodromal DLB group (PRD-DLB) (n = 20) and clinical DLB group (CLIN-DLB) (n = 18) and compared these groups with an Alzheimer's disease control group (AD) (n = 10). PRD-DLB was defined as patients having the non-motor symptoms associated with Lewy body disease (LBD) [i.e. REM sleep behavior disorder (RBD), olfactory dysfunction, autonomic dysfunction, and depression] and showing characteristic diffuse occipital hypometabolism in 18F-FDG PET. CLIN-DLB was defined as patients fulfilling the established criteria of probable DLB. Striatal specific binding ratio (SBR) of 123I-FP-CIT SPECT was used for objective group comparisons. The correlations between SBR and cognitive function (MMSE), motor symptoms (UPDRS3), and duration of LBD-associated non-motor symptoms were compared between the two DLB groups. RESULTS: Mean SBR scores of both PRD-DLB and CLIN-DLB were significantly lower than those of AD. No correlation was found between SBR and MMSE scores. Both in the CLIN-DLB and total DLB groups, SBR scores were negatively correlated with UPDRS3 scores, whereas no correlation was found in PRD-DLB. Among the LBD-related non-motor symptoms, duration of olfactory dysfunction, and RBD demonstrated negative correlation with SBR scores in PRD-DLB. CONCLUSION: 123I-FP-CIT SPECT may play a role for detecting DLB among the subjects in prodromal stage. During this stage, long-term olfactory dysfunction and/or RBD may indicate more severe degeneration of the nigro-striatal dopaminergic pathway.

Clinicopathological characteristics of patients with amyotrophic lateral sclerosis resulting in a totally locked-in state (communication Stage V).

In the present study, we performed a comprehensive analysis to clarify the clinicopathological characteristics of patients with amyotrophic lateral sclerosis (ALS) that had progressed to result in a totally locked-in state (communication Stage V), in which all voluntary movements are lost and communication is impossible. In 11 patients, six had phosphorylated TAR DNA-binding protein 43 (pTDP-43)-immunoreactive (ir) neuronal cytoplasmic inclusions (NCI), two had fused in sarcoma (FUS)-ir NCI, and three had copper/zinc superoxide dismutase (SOD1)-ir NCI. The time from ALS onset to the need for tracheostomy invasive ventilation was less than 24 months in ten patients. Regardless of accumulated protein, all the patients showed common lesions in the pallido-nigro-luysian system, brainstem reticular formation, and cerebellar efferent system, in addition to motor neurons. In patients with pTDP-43-ir NCI, patients with NCI in the hippocampal dentate granule neurons (DG) showed a neuronal loss in the cerebral cortex, and patients without NCI in DG showed a preserved cerebral cortex. By contrast, in patients with FUS-ir NCI, patients with NCI in DG showed a preserved cerebral cortex and patients without NCI in DG showed marked cerebral degeneration. The cerebral cortex of patients with SOD1-ir NCI was preserved. Together, these findings suggest that lesions of the cerebrum are probably not necessary for progression to Stage V. In conclusion, patients with ALS that had progressed to result in communication Stage V showed rapidly-progressed symptoms, and their common lesions could cause the manifestations of communication Stage V.