Dementia in Parkinson's disease: diffusion tensor imaging.

OBJECTIVE: Dementia occurs frequently in patients with Parkinson's disease (PD). However, the nature of the dementing process remains controversial. We evaluated various cognitive functions in patients with PD, compared fractional anisotropy (FA) values between PD patients with and without dementia. METHODS: Thirty-seven consecutive patients with Hoehn-Yahr stage III or IV PD participated in this study. Patients were divided into two groups: (i) PD with dementia group (PDD) and (ii) PD without dementia group (PDND). There were 11 PDD and 26 PDND cases. Ten controls were also studied. RESULTS: The PDD group showed significant FA reduction in the bilateral posterior cingulate bundles compared with PDND. FA values in the left posterior cingulate bundle showed significant correlations with many cognitive parameters. INTERPRETATION: Our results showed that the posterior cingulate areas play some important roles in the dementing process in PDD. However, as the pathological processes responsible for dementia in PD patients may be multifaceted, further studies are necessary.

Wisconsin Card Sorting Test in Parkinson's disease: diffusion tensor imaging.

INTRODUCTION: It is generally assumed that executive dysfunctions in Parkinson's disease (PD) are caused by degeneration of the basal ganglia or frontal cortex or both. However, there have been few studies investigating the relationship between executive dysfunctions and cerebral pathological change. The objective of this study was to evaluate various cognitive functions in non-demented patients with PD, and to compare the fractional anisotropy (FA) values of PD patients with and without executive dysfunction. MATERIALS AND METHODS: Twenty-one consecutive non-demented patients with PD were enrolled in this study. Patients were divided into two groups on the basis of their Wisconsin Card Sorting Test score. RESULTS: There was significant FA reduction in the left parietal white matter in the group in which the number of categories achieved was 2. CONCLUSION: Accumulating evidence suggests that conventional 'frontal' tasks correlate with both frontal lobe and parietal lobe function, and we suggest that pathological changes in the left parietal lobe may cause, in part, disturbances in executive tasks in PD.

Three-dimensional stereotactic surface projection study of orthostatic hypotension and brain perfusion image in Parkinson's disease.

OBJECTIVE: To compare brain perfusion image using three-dimensional stereotactic surface projection (3D-SSP) analysis of N-isopropyl-p-123I iodoamphetamine (123I-IMP) single photon emission computed tomography (SPECT) between patients with Parkinson's disease with orthostatic hypotension and those without orthostatic hypotension. MATERIALS AND METHODS: Fifteen patients with Parkinson's disease and orthostatic hypotension and 13 patients with Parkinson's disease without orthostatic hypotension were studied. We compared brain perfusion image between the two groups by 3D-SSP. RESULTS: Bilateral anterior cingulate gyrus perfusion of the patients with orthostatic hypotension was significantly decreased compared to that of the patients without orthostatic hypotension. CONCLUSIONS: The disorder of anterior cingulate gyrus may participate in the autonomic failure in Parkinson's disease.

CD16+CD57- natural killer cells in multifocal motor neuropathy.

We analyzed the CD16+CD57- lymphocyte subset, which is considered to have strong natural killer (NK) cell activity, in peripheral blood from patients with chronic immune-mediated neuropathies and patients with other neurological diseases. We found that the ratio of CD16+CD57- NK cells to total lymphocytes was increased in 4 of 6 patients with multifocal motor neuropathy (MMN) with persistent conduction block. Since the CD16 molecule is an Fc receptor for immunoglobulin G (IgG), high-dose intravenous immunoglobulin (IVIg) may interfere with CD16+CD57- NK cells via Fc receptor blockade. In addition, cyclophosphamide (Cy) is often used to suppress NK cells. Therefore, our findings may partly account for the effectiveness of IVIg or Cy, which is the current treatment of choice for MMN.

[Cerebral infarction presenting pure motor monoparesis: diagnosis by diffusion-weighted MR imaging].

We studied 10 patients with acute ischemic cerebrovascular disorders presenting paralysis confined to one limb, unaccompanied by sensory signs(pure motor monoparesis, PMM) on diffusion-weighted MR imaging(DWI). DWI revealed fresh ischemic lesions in all patients, except for 2 cases of transient ischemic attack. On DWI, acute infarction in multiple lesions was identified, and small superficial lesions were clearly described. Superficial lesions were seen in 4 patients, and deep lesions were also seen in 4 patients. DWI is useful for lesion analysis in cerebral infarction with PMM.

Genetic analysis of assembly of the Salmonella enterica serovar Typhimurium type III secretion-associated needle complex.

Several pathogenic bacteria have evolved a specialized protein secretion system termed type III to secrete and deliver effector proteins into eukaryotic host cells. Salmonella enterica serovar Typhimurium uses one such system to mediate entry into nonphagocytic cells. This system is composed of more than 20 proteins which are encoded within a pathogenicity island (SPI-1) located at centisome 63 of its chromosome. A subset of these components form a supramolecular structure, termed the needle complex, that resembles the flagellar hook-basal body complex. The needle complex is composed of a multiple-ring cylindrical base that spans the bacterial envelope and a needle-like extension that protrudes from the bacterial outer surface. Although the components of this structure have been identified, little is known about its assembly. In this study we examined the effect of loss-of-function mutations in each of the type III secretion-associated genes encoded within SPI-1 on the assembly of the needle complex. This analysis indicates that the assembly of this organelle occurs in discrete, genetically separable steps. A model for the assembly pathway of this important organelle is proposed that involves a sec-dependent step leading to the assembly of the base substructure followed by a sec-independent process resulting in the assembly of the needle portion.

Molecular characterization and assembly of the needle complex of the Salmonella typhimurium type III protein secretion system.

Many bacterial pathogens of plants and animals have evolved a specialized protein-secretion system termed type III to deliver bacterial proteins into host cells. These proteins stimulate or interfere with host cellular functions for the pathogen's benefit. The Salmonella typhimurium pathogenicity island 1 encodes one of these systems that mediates this bacterium's ability to enter nonphagocytic cells. Several components of this type III secretion system are organized in a supramolecular structure termed the needle complex. This structure is made of discrete substructures including a base that spans both membranes and a needle-like projection that extends outward from the bacterial surface. We demonstrate here that the type III secretion export apparatus is required for the assembly of the needle substructure but is dispensable for the assembly of the base. We show that the length of the needle segment is determined by the type III secretion associated protein InvJ. We report that InvG, PrgH, and PrgK constitute the base and that PrgI is the main component of the needle of the type III secretion complex. PrgI homologs are present in type III secretion systems from bacteria pathogenic for animals but are absent from bacteria pathogenic for plants. We hypothesize that the needle component may establish the specificity of type III secretion systems in delivering proteins into either plant or animal cells.

[A case of acute motor sensory axonal polyneuropathy after Haemophilus influenzae infection].

A 47-year-old woman developed consciousness disturbance, and experienced hallucinations while traveling abroad, and then went into critical condition. She was placed in the critical care unit, and had flaccid tetraparesis requiring mechanical ventilation. Haemophilus influenzae was cultured from the sputum. The level of protein of the cerebrospinal fluid was elevated to 114 mg/dl, nerve conduction study showed findings of pure axonal damage, and the sural nerve biopsy revealed severe axonal degeneration. She improved gradually by plasma exchange. The diagnosis of acute motor sensory axonal polyneuropathy (AMSAN) based on autoimmune mechanism was made. We speculate that H. influenzae infection may have elicited AMSAN in this case.

Combined use of type A and F botulinum toxins for blepharospasm: a double-blind controlled trial.

Type A botulinum toxin has widened its clinical range of applications, but the risk of developing antibodies limits the repeated use of high-dose injection. To minimize the risk, mixing different types of toxin might reduce the antigenic presentation of a specific toxin and associated proteins. At the same time, inhibition of the neuromuscular release process at the multiple sites might potentiate the clinical response or the duration of action. We compared the effectiveness of a mixture of type A and type F botulinum toxins with that of type A or type F toxin alone for treating patients with blepharospasm in a double-blind study. Fifty-four patients had 10 units of toxin injection, a mixture of type A and F toxins (including 5 units of each) on one side and either type A or F toxin on the other side of the orbicularis oculi muscle. Clinical evaluation at 4 and 10 weeks after the injection revealed that the peak clinical effect at 4 weeks was similar among the three preparations. The duration of action of the mixture was intermediate between type A and type F alone, as assessed at 10 weeks, when there was a tendency of conserving the beneficial effect on one eye at the expense of that on the other. Although there was no apparent potentiation of the clinical efficacy, the combination of these different types of toxin might be used for decreasing the risk of antibody development.

Abnormal cortical processing of voluntary muscle relaxation in patients with focal hand dystonia studied by movement-related potentials.

In order to clarify the abnormality in cortical motor preparation for voluntary muscle relaxation of the hand in patients with focal hand dystonia, Bereitschaftspotentials (BPs) preceding voluntary muscle contraction and relaxation were recorded in eight patients (three with simple writer's cramp and five with dystonic writer's cramp), and were compared with those from 10 normal subjects. Voluntary muscle relaxation: after keeping the right wrist in an extended position for > 5 s, the subject let the hand drop by voluntarily terminating muscle contraction of the wrist extensor without any associated muscle contraction. Voluntary muscle contraction: the right wrist was flexed by voluntarily contracting the wrist flexor muscle. Scalp EEGs were recorded from 11 electrodes placed over the frontal, central and parietal areas. In the control group, the BP measured at the movement onset was maximal at the left central area (C1), and distributed predominantly over the left hemisphere equally in both the contraction and relaxation tasks. In the focal hand dystonia group, BP was maximal at C1 in the contraction task, whereas, in the relaxation task, it was maximal at the midline central area (Cz) and symmetrically distributed. At the left central area, the BP amplitude in the focal hand dystonia group was diminished significantly in the relaxation task compared with the contraction task (P < 0.05). The present results demonstrate for the first time that the cortical preparatory process for voluntary muscle relaxation, or motor inhibition, is abnormal in focal hand dystonia.

Abnormal contingent negative variation in writer's cramp.

OBJECTIVE: To investigate the physiological abnormality in writer's cramp, a focal dystonia which specifically affects writing. METHODS: We recorded brain potentials that precede hand and neck movements (contingent negative variation or CNV) in 11 patients and 11 age-matched normal subjects. A 1000 Hz tone burst (S1) was delivered to the right or left ear in random sequence, and 2 s after, a 2000 Hz tone burst (S2) was delivered to both ears simultaneously. For the response task to S2, the subjects were instructed to extend their fingers ipsilateral to the ear to which S1 was given in one experiment or to rotate the head to the side of the S1 presentation in another. All the patients had symptoms in the right hand only, and performed both tasks normally. CNV amplitudes were compared between normals and patients using unpaired t test. RESULTS: They showed normal CNV for neck movement but significantly decreased CNV amplitudes for movements both in the affected and unaffected hands. CONCLUSIONS: Our findings suggest that motor programming is specifically abnormal for the affected body part, including the asymptomatic contralateral limb, and that the clinical symptom may result from a deficient compensatory mechanism for abnormal motor programs or subroutines.

[The clinical usefulness of high-dose intravenous immunoglobulin therapy for chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy].

To explore the optimum dose of intravenous immunoglobulin (i.v.Ig) for treating patients with chronic inflammatory demyelinating polyrneuropathy and multifocal motor neuropathy, we compared the usefulness of i.v.Ig among 3 treatment doses. Fifty-nine patients were randomly divided into three treatment dosage groups: 20 patients for Group I using 50 mg/kg/day x 5 days, 19 patients Group II using 200 mg/kg/day x 5 days, and 20 patients Group III using 400 mg/kg/day x 5 days. We assessed clinically and electrophysiologically the effectiveness of the treatment at 5 weeks after the initial infusion. For patients in Group I and II who had not improved (or worsened) with the first treatment, we gave a one-step larger dose in the second treatment (i.e. 200 mg/kg/day x 5 days for those who had been given 50 mg/kg/day x 5 days, 400 mg/kg/day x 5 days for those who had been given 200 mg/kg/day x 5 days) after more than 9 weeks. We found that 15% of the patients in Group I, 21% in Group II and 60% in Group III improved dose-dependently with the first intravenous immunoglobulin treatment. Seven (47%) of 16 patients in Group I and 4 (40%) of 11 patients in Group II improved after the second treatment with larger doses. Adverse reactions including chill sensation, fever, skin eruption and increase in blood GOT and GPT levels were transient and mild. One patient in Group III developed left hemiparesis showing the small infarction in the right thalamus during the course of the treatment, but the symptom was mild. In conclusion, the high-dose intravenous immunoglobulin therapy (400 mg/kg/day x 5 days) is useful for treating patients with CIDP and MMN, although care must be taken of the risk of causing cerebral infarctions.

[A juvenile case of chronic inflammatory demyelinating polyradiculoneuropathy with severe onion bulb-like change mimicking hereditary neuropathy].

A 15-year-old male developed symmetrical weakness of the limb muscles. He had not had any previous developmental disorders except delayed initiation of walking. Flexion contraction of ankle joint and pes cavus deformity were seen. The cerebrospinal fluid protein concentration was elevated. Nerve conduction study showed severe conduction block and temporal dispersion. A sural nerve biopsy revealed remarkable onion bulb-like changes and perivascular infiltration of inflammatory cells. After high-dose corticosteroid treatment, he showed improvement in muscle strength. Although there were no abnormalities of genes related to hereditary neuropathy, the atypical findings of severe demyelinating changes of peripheral nerves mimicked hereditary neuropathy.

Muscle afferent block for the treatment of oromandibular dystonia.

Oromandibular dystonia is a focal dystonia involving the masticatory and tongue muscles, causing difficulties in speech or mastication. We treated 13 patients with this condition by injecting diluted lidocaine and alcohol intramuscularly. This method is aimed at reducing muscle spindle afferent activity. The symptoms had been resistant to other therapies such as pharmacotherapy or dental treatment. All patients showed clinical improvement after this therapy with reduced EMG activities in the affected muscles, whereas control injection of normal saline gave no changes in EMG activities. The overall subjective improvement was 57.7 +/- 25.1% (mean +/- standard deviation) in a self-rating scale. The mean response of the jaw elevator muscles (70 +/- 13.1%) was significantly higher (p < 0.02, t test) than that of the depressor muscles (38 +/- 28.4%). Despite the precise mechanism being unknown, this difference might be related to the smaller number of muscle spindles in the depressor than the elevator muscles. This therapy is useful for the treatment of drug-resistant oromandibular dystonia.

Supramolecular structure of the Salmonella typhimurium type III protein secretion system.

The type III secretion system of Salmonella typhimurium directs the translocation of proteins into host cells. Evolutionarily related to the flagellar assembly machinery, this system is also present in other pathogenic bacteria, but its organization is unknown. Electron microscopy revealed supramolecular structures spanning the inner and outer membranes of flagellated and nonflagellated strains; such structures were not detected in strains carrying null mutations in components of the type III apparatus. Isolated structures were found to contain at least three proteins of this secretion system. Thus, the type III apparatus of S. typhimurium, and presumably other bacteria, exists as a supramolecular structure in the bacterial envelope.

Flagellar filament elongation can be impaired by mutations in the hook protein FlgE of Salmonella typhimurium: a possible role of the hook as a passage for the anti-sigma factor FlgM.

Among motile revertants isolated from flagellar hook-deficient (flgE) mutants of Salmonella typhimurium, one produced only short flagellar filaments in L broth, despite the fact that flagellin itself has the ability to polymerize into long filaments in vitro. This pseudorevertant has an intragenic suppressor, resulting in a two-amino-acid substitution (Asp-Gln-->Ala-Arg) in the C-terminal region of the hook protein, FlgE. The flagellation of the pseudorevertant was greatly affected by the concentration of NaCl in the culture media: we observed no filaments in the absence of NaCl, short filaments in 1% NaCl and full-length filaments in 2% NaCl. Electron microscopy of osmotically shocked cells showed that the number of hook-basal bodies on cells was constant under various NaCl conditions. Furthermore, we found that the mutant hook was straight rather than curved. We monitored the cellular flagellin level of this pseudorevertant under various NaCl concentrations by immunoblotting. It was revealed that little flagellin was present under NaCl-free conditions in contrast with the ordinary amounts of flagellin present in 2% NaCl. As the expression of flagellin is regulated by competitive interaction of a sigma factor, FliA, and a corresponding anti-sigma factor, FlgM, we also observed the effect of NaCl on the secretion of FlgM. FlgM was secreted into the media in more than 1% NaCl but accumulated inside the cells in the absence of NaCl, indicating that the failure of secretion of FlgM in the absence of salt was the cause of the impaired elongation of filaments.

Bacterial flagellation and cell division.

The peritrichous flagella of Salmonella are synthesized and function through many cell generations. There are two different aspects in the relationship between flagellar biogenesis and cell division. Filament growth is independent from the cell cycle and the length of filaments appear to be locally controlled at each flagellar base, whereas the number of filaments (or flagellar basal bodies) is dependent on cell cycle. We present a model to explain how the number of filaments is maintained through generations. We will also introduce a new direction for research that might directly connect flagellation and cell division; the global communication between flagellar genes and external factors of a complex regulatory network in a cell.