Pathology and sensitivity of current clinical criteria in corticobasal syndrome

The aim of this study was to investigate corticobasal syndrome with respect to underlying pathologies, the ability of current clinical criteria to detect early stages of disease, and symptoms and signs predicting background pathologies. We retrospectively analyzed the clinicopathological findings from patients with corticobasal syndrome. We also analyzed whether those findings fulfilled the diagnostic criteria for corticobasal degeneration (CBD). Finally, we investigated characteristic clinical features that are specific to each background pathology. Of 10 consecutive autopsied patients who had corticobasal syndrome (mean age ± standard deviation, 67.9 ± 9.3 years; male:female ratio, 6:4), three had corticobasal degeneration pathology, three had progressive supranuclear palsy, three had Alzheimer's disease, and one had atypical four‐repeat tauopathy. Nine patients fulfilled Mayo criteria, and all 10 patients fulfilled modified Cambridge criteria at the later stage, but only two patients fulfilled either clinical criteria within 2 years of disease onset. Five patients fulfilled the clinical criteria for possible CBD (p‐CBD), and one patient fulfilled the clinical research criteria for probable sporadic CBD (cr‐CBD) at the later stage. Only two patients fulfilled the criteria for either p‐CBD or cr‐CBD within 2 years of disease onset. Although we could not find any predictive characteristic clinical features that were specific to CBD pathology, only patients with progressive supranuclear palsy developed apraxia of eyelid opening and cerebellar ataxia. Myoclonus and memory impairment, especially if they appear at an early stage of the disease, may predict Alzheimer's disease pathology. Sensitivity of the available clinical criteria for corticobasal syndrome was poor within 2 years of disease onset. © 2013 International Parkinson and Movement Disorder Society     

Girl with a PRRT2 mutation and infantile focal epilepsy with bilateral spikes

This paper documents the case of a female Japanese patient with infantile focal epilepsy, which was different from benign infantile seizures, and a family history of infantile convulsion and paroxysmal choreoathetosis. The patient developed partial seizures (e.g., psychomotor arrest) at age 14 months. At the time of onset, interictal electroencephalography (EEG) showed bilateral parietotemporal spikes, but the results of neurologic examination and brain magnetic resonance imaging were normal. Her seizures were well controlled with carbamazepine, and she had a normal developmental outcome. EEG abnormalities, however, persisted for more than 6 years, and the spikes moved transiently to the occipital area and began to resemble the rolandic spikes recognized in benign childhood epilepsy. Her father had paroxysmal kinesigenic dyskinesia, with an onset age of 6 years, and her youngest sister had typical benign infantile seizures. Genetic analysis demonstrated that all affected members had a heterozygous mutation of c.649_650insC in the proline-rich transmembrane protein-2 (PRRT2) gene. This case indicates that the phenotypic spectrum of infantile seizures or epilepsy with PRRT2-related pathology may be larger than previously expected, and that genetic investigation of the effect of PRRT2 mutations on idiopathic seizures or epilepsy in childhood may help elucidate the pathological backgrounds of benign childhood epilepsy.     

Astrocytic activation in the anterior cingulate cortex is critical for sleep disorder under neuropathic pain

Insomnia, depression, and anxiety disorder are common problems for people with neuropathic pain. In this study, mild noxious heat stimuli increased the duration and number of spontaneous pain‐like behaviors in sciatic nerve‐ligated mice. We used functional magnetic resonance imaging to visualize the increased blood oxygenation level‐dependent signal intensity in the anterior cingulate cortex (ACC) of mice with sciatic nerve ligation under mild noxious stimuli. Such stimuli significantly increased the release of glutamate in the ACC of nerve‐ligated mice. In addition, sciatic nerve ligation and mild noxious stimuli changed the morphology of astrocytes in the ACC. Treatment of cortical astrocytes with glutamate caused astrocytic activation, as detected by a stellate morphology. Furthermore, glutamate induced the translocation of GAT‐3 to astrocyte cell membranes using primary cultured glial cells from the mouse cortex. Moreover, the GABA level at the synaptic cleft in the ACC of nerve‐ligated mice was significantly decreased exposure to mild noxious stimuli. Finally, we investigated whether astrocytic activation in the ACC could directly mediate sleep disorder. With the optogenetic tool channel rhodopsin‐2 (ChR2), we demonstrated that selective photostimulation of these astrocytes in vivo triggered sleep disturbance. Taken together, these results suggest that neuropathic pain‐like stimuli activated astrocytes in the ACC and decreased the extracellular concentration of GABA via an increase in the release of glutamate. Furthermore, these findings provide novel evidence that astrocytic activation in the ACC can mimic sleep disturbance in mice. Synapse 68:235–247, 2014 . © 2014 Wiley Periodicals, Inc.     

Bunina bodies in motor and non‐motor neurons revisited: A pathological study of an ALS patient after long‐term survival on a respirator

Bunina bodies (BBs) are small eosinophilic neuronal cytoplasmic inclusions (NCIs) found in the remaining lower motor neurons (LMNs) of patients with sporadic amyotrophic lateral sclerosis (SALS), being a specific feature of the cellular pathology. We examined a case of SALS, unassociated with TDP‐43 or C9ORF72 mutation, of 12 years duration in a 75‐year‐old man, who had received artificial respiratory support for 9 years, and showed widespread multisystem degeneration with TDP‐43 pathology. Interestingly, in this patient, many NCIs reminiscent of BBs were observed in the oculomotor nucleus, medullary reticular formation and cerebellar dentate nucleus. As BBs in the cerebellar dentate nucleus have not been previously described, we performed ultrastructural and immunohistochemical studies of these NCIs to gain further insight into the nature of BBs. In each region, the ultrastructural features of these NCIs were shown to be identical to those of BBs previously described in LMNs. These three regions and the relatively well preserved sacral anterior horns (S1 and S2) and facial motor nucleus were immunostained with antibodies against cystatin C (CC) and TDP‐43. Importantly, it was revealed that BBs exhibiting immunoreactivity for CC were a feature of LMNs, but not of non‐motor neurons, and that in the cerebellar dentate nucleus, the ratio of neurons with BBs and TDP‐43 inclusions/neurons with BBs was significantly lower than in other regions. These findings suggest that the occurrence of BBs with CC immunoreactivity is intrinsically associated with the particular cellular properties of LMNs, and that the mechanism responsible for the formation of BBs is distinct from that for TDP‐43 inclusions.     

Extraduodenal Papillectomy: a Feasible Alternative Method of Total Papillectomy

Rational treatment for neoplasms of the duodenal papilla (NDPs) is still controversial, especially for early stage lesions. Total papillectomies are indicated in patients expected to have adenomas, adenocarcinoma in an adenoma, or mucosal adenocarcinomas with no lymph node metastases. However, the preoperative pathological evaluation of NDPs is still challenging and often inaccurate, mainly because of the complicated anatomical structures involved and the possibility of an adenocarcinoma in an adenoma. Herein, we introduce a new method of total papillectomy, the extraduodenal papillectomy (ExDP). In this method, papillectomy is undertaken from outside of the duodenum, instead of resection from the inside through a wide incision of the duodenal wall as is done in conventional transduodenal papillectomy (TDP). The advantages of ExDP are precise and deeper cutting of the sphincter and shorter exploration time of the tumor compared to conventional TDP. We demonstrate three representative patients, all of whom had an uneventful postoperative course. One of them subsequently underwent a pylorus preserving pancreatoduodenectomy after detailed postoperative pathological evaluation. Including that patient, no recurrence has occurred with 37–46 months of follow-up. In conclusion, ExDP is regarded as a “total biopsy” for early stage borderline lesions and a feasible, less demanding alternative method for the treatment of NDPs.     

Diagnostic criteria for atypical hemolytic uremic syndrome proposed by the joint committee of the Japanese society of nephrology and the Japan pediatric society

Atypical hemolytic uremic syndrome (aHUS) is rare and comprises the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. Recently, abnormalities in the mechanisms underlying complement regulation have been focused upon as causes of aHUS. The prognosis for patients who present with aHUS is very poor, with the first aHUS attack being associated with a mortality rate of ~25 %, and with ~50 % of cases resulting in end-stage renal disease requiring dialysis. If treatment is delayed, there is a high risk of this syndrome progressing to renal failure. Therefore, we have developed diagnostic criteria for aHUS to enable its early diagnosis and to facilitate the timely initiation of appropriate treatment. We hope these diagnostic criteria will be disseminated to as many clinicians as possible and that they will be used widely.     

Kinematic and Kinetic Profiles of Trunk and Lower Limbs during Baseball Pitching in Collegiate Pitchers

The purpose of this study was to clarify differences in the kinematic and kinetic profiles of the trunk and lower extremities during baseball pitching in collegiate baseball pitchers, in relation to differences in the pitched ball velocity. The subjects were 30 collegiate baseball pitchers aged 18 to 22 yrs, who were assigned to high- (HG, 37.4 ± 0.8 m·s^-1) and low-pitched-ball-velocity groups (LG, 33.3 ± 0.8 m·s^-1). Three-dimensional motion analysis with a comprehensive lower-extremity model was used to evaluate kinematic and kinetic parameters during baseball pitching. The ground-reaction forces (GRF) of the pivot and stride legs during pitching were determined using two multicomponent force plates. The joint torques of hip, knee, and ankle were calculated using inverse-dynamics computation of a musculoskeletal human model. To eliminate any effect of variation in body size, kinetic and GRF data were normalized by dividing them by body mass. The maxima and minima of GRF (Fy, Fz, and resultant forces) on the pivot and stride leg were significantly greater in the HG than in the LG (p < 0.05). Furthermore, Fy, Fz, and resultant forces on the stride leg at maximum shoulder external rotation and ball release were significantly greater in the HG than in the LG (p < 0.05). The hip abduction, hip internal rotation and knee extension torques of the pivot leg and the hip adduction torque of the stride leg when it contacted the ground were significantly greater in the HG than in the LG (p < 0.05). These results indicate that, compared with low-ball-velocity pitchers, high-ball-velocity pitchers can generate greater momentum of the lower limbs during baseball pitching.

Key points

• High-ball-velocity pitchers are characterized by greater momentum of the lower limbs during pitching motion.
• For high-pitched-ball velocity, stabilizing lower limbs during pitching plays an important role in order to increase the rotation and forward motion of the trunk.
• Computation of the lower-extremity kinetics and measurement of lower-extremity strength may help clarify the role of muscle strength in determining knee and hip function in baseball pitching.

Key words: Throwing movement, pitching ball velocity, ground-reaction force, lower limbs, pivot and stride legs     

Retraction-Related Acute Liver Failure after Urological Laparoscopic Surgery

Liver retraction is necessary for optimal exposure during laparoscopic right renal surgery. We described a patient who developed fulminant liver failure as a result of liver retractor-induced excessive ischemic changes in the right lobe of the liver. A 37-year-old male underwent a right side laparoscopic pyeloplasty for ureteropelvic junction obstruction. At the beginning of the operation, a small snake retractor was placed through a 5-mm port under direct vision. The liver was lifted in the appropriate direction to optimize exposure by using the laparoscope holder. The operation was prolonged. However, we achieved significant improvements in the efficiency of liver retraction using the holder. On the first postoperative day, the patient''s serum levels of GOT, GPT and LDH had remarkably increased. A computerized tomogram confirmed the presence of excessive ischemic changes of the right lobe of the liver. Our method which used a laparoscope holder device for liver retraction maintained a better surgical field. However, neglecting to make minor adjustments to the positioning of the retractor can cause significant pressure on the liver parenchyma in a single area. As surgical procedures increase in complexity, the surgeon should keep these potential side effects in mind and shift the retraction point at regular intervals. In this report, we discussed various types of retractor-related liver injuries and their management, and highlighted the importance of intermittent release of retraction during prolonged surgery.Key Words: Laparoscopic surgery, Liver injury, Retractor, Acute liver failure