Is temporomandibular joint involvement more frequent in patients with epilepsy? A clinical study.

STATEMENT OF PROBLEM: Epileptic seizures may affect the stomatognathic system via transmission of an increased load to the dentition and the temporomandibular joint (TMJ), resulting in temporomandibular joint dysfunction (TMD). PURPOSE: The purpose of this clinical study was to assess whether TMD was more prevalent in patients with epilepsy than in those without epilepsy. MATERIAL AND METHODS: A total of 107 participants diagnosed with epilepsy and 100 healthy controls were enrolled in the study. Those with epilepsy were divided according to their dental manageability into 3 subgroups: mild group, moderate group, and severe group. Following general, dental, and TMJ-related history, the range of maximal mouth opening (MMO), laterotrusion, possible deviation and deflection, and presence of crepitation and clicking was recorded, as suggested by the diagnostic criteria for temporomandibular diseases (DC/TMD). Pressure pain threshold (PPT) was also measured by using a pressure algometer on 3 points bilaterally. RESULTS: Incidence of TMJ complaints was not significantly different between the control (30%) and the group diagnosed with epilepsy (33%); however, the number of complaints experienced was significantly higher in the epilepsy group (C: 3%, E: 16% had 3 or more complaints; P<.001). Joint clicking was significantly more prevalent in the entire epilepsy group (P=.012) and in the mild group (P=.004) than in controls. Crepitation and joint pain were not significantly more common in the epilepsy group. Maximal mouth opening, laterotrusion, and the ratio of restricted mouth opening did not differ significantly in the epilepsy group. Deflection occurred significantly more often in the epilepsy subgroups (mild and moderate groups; P<.001), and the extent of deflection was also significantly higher in all the epilepsy subgroups (P<.001) than in controls. Regarding the pressure pain threshold, significant difference was observed in the severe group at the left masseter muscle points M1 (P=.046) and M2 (P=.028) compared with controls. CONCLUSIONS: All parameters typical of TMD could be found frequently in patients with epilepsy. Because of the seizures and the consequent joint overload, the TMJ involvement was more common or more serious in those diagnosed with epilepsy. Outcomes of this study support the assumption that epilepsy is a risk factor for the development of TMD.

Variant Transthyretin Amyloidosis (ATTRv) in Hungary: First Data on Epidemiology and Clinical Features.

BACKGROUND: Variant transthyretin amyloidosis (ATTRv) is an autosomal dominant inherited disease, where the mutation of the transthyretin gene (TTR) results in the deposition of pathogenic protein fibrils in various tissues. The mutation type influences the clinical course. Until now, no data were available on the genotype, phenotype, and prevalence of Hungarian ATTRv patients. The aim of our study was to assess the prevalence, regional distribution, genotypes, and phenotypes of Hungarian patients with ATTRv. METHODS: With the collaboration of Hungarian regional and university centers, we identified patients diagnosed with ATTRv. We also searched prior publications for case studies of Hungarian ATTRv patients. RESULTS: 40 individuals in 23 families with ATTRv were identified within the borders of Hungary. At the time of the diagnosis, 24 of them were symptomatic. The two most common mutations were ATTRHis88Arg (nine families) and ATTRIle107Val (8 families). ATTRVal30Met was demonstrated in 2 families, and ATTRVal122del, ATTRPhe33Leu, ATTRIle84Ser, and ATTRAsp18Gly in one family each. The median age of the symptomatic patients at the time of clinical diagnosis was 65 years. The most common clinically significant organ involvement was restrictive cardiomyopathy, found in 24 patients. Polyneuropathy was diagnosed in 20 patients. A total of 19 patients showed a mixed phenotype. The leading symptom was heart failure in 8 cases (3 of them had only cardiac symptoms), polyneuropathy in 11 cases (all of them also had cardiac symptoms), and equally severe cardiac and neuropathy symptoms were present in 3 cases. Out of 24 symptomatic patients, 10 received targeted pharmacological therapy. The follow-up period ranged from 1 to 195 months. At the time of the retrospective analysis, 12 patients had already died, and 1 patient underwent heart transplantation. CONCLUSIONS: As TTR genotype influences the phenotype and clinical course of ATTRv, it is important to know the regional data. In Hungary, ATTRHis88Arg and ATTRIle107Val are the most common mutations in ATTRv, both presenting with mixed phenotype, but the median age at the time of the diagnosis is 9 years lower in patients with ATTRHis88Arg than in patients with ATTRIle107Val.

[Serum biomarkers in acute low back pain and sciatica]. / Szérumbiomarkerek akut lumbalis-lumbosacralis fájdalomban.

Inflammation contributes to the pathogenesis of low back pain and sciatica. Growing evidence suggests that elevated levels of some inflammatory biomarkers are associated with these conditions. Much of the research evaluating the association between pro- and anti-inflammatory cytokines, chemokines, other regulatory molecules, and low back pain and sciatica, focused on patients with chronic low back pain, while fewer studies addressed the issue of detectable biomarkers in the acute phase. Previous studies suggest that pro-inflammatory cytokines such as TNF-α, IL-6, and IL-8 and anti-inflammatory IL-4 and IL-10 play an important role in the inflammatory response following intervertebral disc herniation. According to the approach of personalized medicine it is important to identify subsets of patients within the acute patient group regarding etiology, prognosis and treatment. In addition, if we can identify subgroups based on levels of pro-inflammatory biomarkers, where inflammation may be the leading cause of pain, we assume that this subgroup would likely be effectively treated with anti-inflammatory medication. The efficacy of TNF-α inhibitors and IL-6 inhibitors in treating low back pain and sciatica has already been tested in clinical trials, but further studies are required. Overall, identification of circulating biomarkers of acute low back pain and sciatica may assist in refining personalized diagnosis and treatment. Further research is needed to evaluate the role of inflammation in acute low back pain and sciatica, to identify what methods are appropriate for evaluation in clinical practice, and whether there are biomarkers of prognostic value in these patients. Orv Hetil. 2020; 161(13): 483-490.

Ultrasonographic demonstration of intraneural neovascularization after penetrating nerve injury.

INTRODUCTION: Hypervascularization of nerves has been shown to be a pathological sign in some peripheral nerve disorders, but has not been investigated in nerve trauma. METHODS: An observational cohort study was performed of the intraneural blood flow of 30 patients (34 nerves) with penetrating nerve injuries, before or after nerve reconstruction. All patients underwent electrophysiological assessment, and B-mode and color Doppler ultrasonography. RESULTS: Intraneural hypervascularization proximal to the site of injury was found in all nerves, which was typically marked and had a longitudinal extension of several centimeters. In 6 nerves, some blood flow was also present within the injury site or immediately distal to the injury. No correlation was found between the degree of vascularization and age, size of the scar / neuroma, or degree of reinnervation. DISCUSSION: Neovascularization of nerves proximal to injury sites appears to be an essential element of nerve regeneration after penetrating nerve injuries. Muscle Nerve 57: 994-999, 2018.

Ultrasonography in neuralgic amyotrophy: Sensitivity, spectrum of findings, and clinical correlations.

INTRODUCTION: The aim of this study was to assess the value of ultrasonography in neuralgic amyotrophy. METHODS: Fifty-three patients with 70 affected nerves were examined with high-resolution ultrasound. RESULTS: The most commonly affected nerve was the anterior interosseous (23%). Ultrasonographic abnormalities in the affected nerves, rather than in the brachial plexus, were observed, with an overall sensitivity of 74%. Findings included the swelling of the nerve/fascicle with or without incomplete/complete constriction and rotational phenomena (nerve torsion and fascicular entwinement). A significant difference was found among the categories of ultrasonographic findings with respect to clinical outcome (P = 0.01). In nerves with complete constriction and rotational phenomena, reinnervation was absent or negligible, indicating surgery was warranted. DISCUSSION: Ultrasonography may be used as a diagnostic aid in neuralgic amyotrophy, which was hitherto a clinical and electrophysiological diagnosis, and may also help in identifying potential surgical candidates. Muscle Nerve 56: 1054-1062, 2017.

The significance of ultrasonographic carpal tunnel outlet measurements in the diagnosis of carpal tunnel syndrome.

OBJECTIVE: A retrospective study to investigate the utility of ultrasonographic carpal tunnel outlet measurements in the diagnosis of carpal tunnel syndrome (CTS). METHODS: 118 hands of 87 patients with electrophysiologically confirmed CTS and 44 control hands of 23 subjects were assessed. Cross-sectional areas (CSA) of the median nerve were measured at the tunnel inlet, outlet, and forearm. Longitudinal diameters (LAPD) were measured at the inlet, proximal tunnel, distal tunnel, and outlet. RESULTS: CSA at the outlet (median: 18mm2) and its palm-to-forearm-ratio (median: 2.7) were significantly larger than CSA at the inlet (median: 15mm2) and its wrist-to-forearm-ratio (median: 2.2) (p<0.001). 27% of the hands showed enlargement only at the outlet versus 13% only at the inlet. LAPD jump was significantly greater, suggesting relief of higher pressure, at the outlet/distal tunnel versus inlet/proximal tunnel (p<0.001). CONCLUSION: Median nerve enlargement in CTS is greater at the tunnel outlet than at the inlet. We postulate that this is explained by the progressive increase of pressure within the tunnel from proximal to distal. SIGNIFICANCE: The addition of CSA outlet measurements to inlet measurements increased CTS ultrasonographic diagnostic sensitivity and accuracy by 15% and 10%, respectively.

Ultrasonographic Identification of Fibromuscular Bands Associated with Neurogenic Thoracic Outlet Syndrome: The "Wedge-Sickle" Sign.

Thoracic outlet syndrome (TOS) is a disorder characterized by compression of the lower trunk of the brachial plexus, most often in association with anomalous congenital fibromuscular bands in the scalenic region. Early diagnosis is important, because the neurologic deficit associated with TOS may be irreversible. Using high-resolution ultrasound, we investigated 20 consecutive patients with clinical signs suggestive of TOS (all females, average age: 40.4 ± 14.9 y) and 25 control patients. In 19 patients, we identified a hyper-echoic fibromuscular structure at the medial edge of the middle scalene muscle, which indented the lower trunk of the brachial plexus ("wedge-sickle sign"). It was associated with the significant enlargement (p < 0.0001) and hypo-echogenicity of the lower trunk. This novel and distinctive ultrasonographic sign allows pre-surgical identification of anomalous fibromuscular bands causing TOS. It is especially useful in patients without neurologic deficit, in whom the diagnosis may not be as straightforward.

[Transthyretin familial amyloid polyneuropathy - three Hungarian cases with rare mutations (His88Arg and Phe33Leu)]. / Transthyretin familiáris amyloid polyneuropathia - három magyarországi eset ritka mutációkkal (His88Arg és Phe33Leu).

Introduction - Transthyretin familial amyloid polyneuropathy is a rare autosomal dominant progressive systemic disesase of adults caused by endoneural amyloid deposition due to point mutations of the transthyretin gene. It is the most severe form among hereditary polyneuropathies, being fatal within 10 years if left untreated. The disease is underdiagnosed, the late onset forms (above the age of 50) being probably more widespread than previously thought. Early diagnosis is essential as the early introduction of causal therapy (tafamidis) slows progression and prolongs survival. Patients - We report here three non-related Hungarian cases of transthyretin familial amyloid polyneuropathy with non-Val30Met mutations (His88Arg in two cases, Phe33Leu in one case). They were all characterized by late-onset, progressive, length-dependent, axonal, sensorimotor polyneuropathy and the simultaneous presentation of severe restrictive cardiomyopathy. In all three cases, clinical and electrophysiological signs of myopathy were also present, suggesting the involvement of skeletal muscles as well. In two cases, high resolution ultrasound of the peripheral nerves was also performed, which showed segmental structural alterations (change or loss of fascicular structure) and some increase of echogenicity of the interfascicular epineurium, without substantial enlargement of the nerves. Conclusion - In Hungary, mainly the rare, non-Val30Met mutation forms of transthyretin familial amyloid polyneuropathy are encountered, as in our cases. As opposed to the Val30Met forms, these mutations are characterized by late onset and simultaneous presentation of severe cardiomyopathy. Our report highlights the importance of considering transthyretin familial amyloid polyneuropathy in the differential diagnosis of late-onset, progressive, axonal polyneuropathies of unknown etiology, particularly if associated with cardiac disease.

Ultrasonographic identification of nerve pathology in neuralgic amyotrophy: Enlargement, constriction, fascicular entwinement, and torsion.

INTRODUCTION: The aim of this study was to characterize the ultrasonographic findings on nerves in neuralgic amyotrophy. METHODS: Fourteen patients with neuralgic amyotrophy were examined using high-resolution ultrasound. RESULTS: Four types of abnormalities were found: (1) focal or diffuse nerve/fascicle enlargement (57%); (2) incomplete nerve constriction (36%); (3) complete nerve constriction with torsion (50%; hourglass-like appearance); and (4) fascicular entwinement (28%). Torsions were confirmed intraoperatively and were seen on the radial nerve in 85% of patients. A significant correlation was found between no spontaneous recovery of nerve function and constriction/torsion/fascicular entwinement (P = 0.007). CONCLUSION: Ultrasonographic nerve pathology in neuralgic amyotrophy varies in order of severity from nerve enlargement to constriction to nerve torsion, with treatment ranging from conservative to surgical. We postulate that the constriction caused by inflammation is the precursor of torsion and that development of nerve torsion is facilitated by the rotational movements of limbs.

[Complex tremor analysis for the differential diagnosis of essential tremor and Parkinson's disease]. / Komplex tremorometria az esszenciális tremor es a Parkinson-szindróma elkülönítésében.

OBJECTIVE: Tremor is the most common movement disorder which is most often either essential or caused by Parkinson's disease. The differentiation of these disorders at the initial stage may be difficult. Objective assessment of the efficacy of tremor medications is only possible by instrumental measurements. The aim of this study was to determine whether the computer assisted tremor analysis system CATSYS 2000 can help in the differentiation of parkinsonian from essential tremor. METHODS: The rhythmicity and maximal frequency of fast alternating hand and finger movements, simple reaction time and postural instability were recorded in healthy controls (n = 18), patients with Parkinson's disease (n = 39) and essential tremor (n = 37). Data were digitally converted and statistically analyzed. RESULTS: Tremor intensity, median frequency and frequency distribution showed characteristic differences in the three groups. Performance in fast alternating movements of hands and fingers were significantly worse in both tremor groups compared to the healthy controls. CONCLUSIONS: The data also indicated that quantitative measurements of tremor parameters must be performed on both sides, because the presence of significant side differences support the diagnosis of Parkinson's disease. The method presented can be used to objectively analyze tremor and performance in rhythmic movements. The results show that it helps to differentiate parkinsonian from essential tremor as well as to predict disease course and the effectiveness of therapy. Multivariate statistical analysis of tremor and movement performance also provides an opportunity to study the pathogenesis of human tremor.

Asymmetry of tremor intensity and frequency in Parkinson's disease and essential tremor.

We investigated the asymmetry of tremor intensity, frequency and frequency dispersion of Parkinsonian (PT) and essential (ET) tremor using accelerometry. Data of the more and less trembling hands were statistically elaborated. We found that tremor intensity was significantly asymmetric not only in PT but also in ET, while frequency and frequency dispersion were symmetric in ET but asymmetric in PT. We conclude that bilateral assessment of frequency related tremor parameters may be used for differentiation between ET and PT, and provides further details on the central organization of tremor generators.

Asymptomatic cerebellar atrophy after acute enteroviral encephalitis.

We report on a 13-year-old male who had acute enteroviral encephalitis causing cerebellar symptoms at the age of 10 years. Magnetic resonance imaging (MRI) showed no abnormalities. Clinically he appeared to be recovered completely after 6 months. Twenty-three months after the recovery, MRI was performed because he presented with slight lower-limb and truncal ataxia experienced as lack of foot coordination while playing football or riding a bicycle. MRI demonstrated severe cerebellar atrophy. Clinically he recovered completely in 10 days. Only sophisticated electrophysiological methods revealed cerebellar dysfunction. The case provides evidence for the plasticity of cerebellar regulatory structures involved in the coordination of fine movements. It seems that in childhood the slow, isolated disintegration of cerebellar systems can be compensated for by upper thalamic or telencephalic connections, in a similar way to a congenital deficit of the cerebellum.

Effect of 3-nitropropionic acid on kynurenine aminotransferase in the rat brain.

Activation of excitatory amino acid receptors by endogenous excitotoxins results in degenerative changes characteristic of neurodegenerative brain diseases such as Huntington's disease. Excitatory amino acid receptors are present in the highest concentration in the striatum, the hippocampal region, and the temporal lobe. The most potent, naturally occurring excitatory amino acid receptor antagonist is kynurenic acid (KYNA) which acts preferentially on N-methyl-D-aspartate (NMDA) receptors. KYNA is produced from L-kynurenine, by the action of the enzymes kynurenine aminotransferases (KAT I and KAT II). Several inhibitors of mitochondrial energy metabolism result in an indirect excitotoxic neuronal degeneration. We examined whether systemic administration of the mitochondrial toxin 3-nitroproprionic acid (3-NP), an irreversible inhibitor of succinate dehydrogenase, which also acts by an indirect excitotoxic mechanism, would produce alterations in the immunohistochemical pattern of KAT I. Our present investigations demonstrate that after 15 days of administration of 3-NP, an inhibitor of mitochondrial Complex II, the most severe depletion of KAT I occurred in the striatum; less severe depletion occurred in other brain areas investigated, following a striatum > hippocampus > temporal cortex gradient. The alterations induced by 15 days of 3-NP treatment were less conspicuous in 6-week-old (young) animals than in 3-month-old adults. In these adult animals, 3-NP induced necrotic cores in the striatum, characterized by destruction of neuronal and glial elements, similar to that seen in the histologic and neurochemical features of Huntington's disease. It appears that immunohistochemical depletion of KAT after administration of 3-NP to adult animals may contribute to the pathological processes that characterize Huntington's disease.

Expression of kynurenine aminotransferase in the subplate of the rat and its possible role in the regulation of programmed cell death.

The neurons of the transient subplate zone, considered important for the prenatal development of the cerebral cortex, were shown here to express kynurenine aminotransferase (KAT)-I from embryonic day (E) 16 until postnatal day (P) 7 in the rat. No other cells of brain tissue exerted KAT-I immunoreactivity during this period. From P3 on, the neurons of the subplate gave rise to KAT-I immunoreactive, varicose axons, which entered the thalamus and terminated around thalamic nerve cells that are devoid of KAT-I immunoreactivity. Other subplate markers displayed a different expression pattern during development. Thus, subplate neurons displayed parvalbumin (PV) immuno-reactivity from E16 to P10 and an intense NPY immunoreaction from P7 to P1. They also exhibited nitric oxide synthase immunoreactivity from E16 to P10, whereas on the surface of the subplate neurons, the alpha7 subunit of the nicotinic acetylcholine receptor (nAChR) was present from P1 to P10. The cells of Cajal-Retzius were nAChR-immunoreactive during this period. Between P1 and P7, the perikarya of subplate neurons also showed an intense immuno-reaction with the N-methyl-D-aspartate (NMDA) receptor subtype R2A. After the first postnatal week, many of the KAT-I positive subplate neurons display a gradual decrease of immunoreactivity and undergo programmed cell death. Since KAT-I persists in the subplate through the period E16-P7, we conclude that KAT-I is a useful and reliable subplate marker in the rat. Since it is assumed that migration of nerve cells is regulated by NMDA receptors, and since kynurenic acid--the only naturally occurring NMDA receptor antagonist--is synthesized by KAT, we suggest that a temporary breakdown of the delicate equilibrium between NMDA and KAT might induce abnormal neuronal migration, giving rise to developmental abnormalities.