The importance of neurotropic vitamins in the prevention and adjuvant therapy of peripheral neuropathy - A pharmacist's comprehensive view Peripheral neuropathy is one of the most common neurological diseases of the peripheral nervous system. According to current statistics, it affects 2.4% of the Czech population, and its prevalence continues to increase with age. The possibilities of its treatment are to a large extent limited, and its effectiveness and the patient's tolerance of pharmacotherapy are individual. Neurotropic vitamins, which support the function of neurons and contribute to their protection and regeneration, represent a promising possibility for prevention and use in adjuvant therapy for patients suffering from this disease. Despite the fact that the diagnosis and treatment of peripheral neuropathy belong to the doctor, the role of the pharmacist can be crucial not only in the area of ensuring effective and safe pharmacotherapy and adherence to it, but also in pre-screening of at-risk persons visiting pharmacies. The primary aim of the article is therefore to familiarize readers with the significance of neurotropic vitamins in the prevention and adjunct therapy of peripheral neuropathy, as well as the role of the pharmacist in the care of patients suffering from this condition.

• Klíčová slova
• Peripheral neuropathy, Pharmaceutical Care, neurotropic vitamins,
• MeSH
• farmaceuti * MeSH
• lidé MeSH
• nemoci periferního nervového systému * prevence a kontrola   farmakoterapie   MeSH
• role odborníka MeSH
• vitaminy * terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• vitaminy * MeSH

Whipples disease is a chronic multisystem inflammatory disease with predominantly gastrointestinal manifestations due to Tropheryma whipplei infection. Typical neurological abnormalities include dementia, eye movement abnormalities, hypothalamic dysfunction and oculomasticatory myorhythmias. The literature on peripheral neuropathy in Whipples disease is sparse and the involvement of peripheral nerves in Whipples disease has not been documented convincingly so far. We present a case of Whipples disease presenting by axonal peripheral neuropathy without gastrointestinal involvement. The diagnosis was confirmed by a sural nerve biopsy and consequent PCR of the sample. All clinical signs disappeared progressively during the antibiotic therapy. Two years after the T. whipplei infection, the patient developed dopa-sensitive Parkinson's disease, although these two events seem to be unrelated. This case illustrates the value of peripheral nerve biopsy in cases of axonal neuropathy of unexplained origin and extends the clinical spectrum of Whipples disease to a new modality.

• MeSH
• lidé středního věku MeSH
• lidé MeSH
• nemoci periferního nervového systému etiologie   patologie   MeSH
• periferní nervy patologie   MeSH
• Whippleova nemoc komplikace   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

BACKGROUND: Recent studies suggest an increased frequency of peripheral neuropathy (PN) in Parkinson's disease patients (PD) (Toth et al. 2010). The aim of our study is to verify the increased frequency of PN in our group of PD patients compared to an age-matched control group. We sorted patients according to the duration of L-DOPA treatment, L-DOPA dosage, and age below or over 50 years. METHODS AND RESULTS: We conducted electromyography examinations (using conduction studies and needle electromyography) of 49 PD patients with asymptomatic polyneuropathy and 40 controls. Patients without risk factors for PN were included (fasting blood was analyzed to rule out possible causes of PN), as were relatively healthy controls without risk factors for PN. PN was defined using the American Academy of Neurology and Electrodiagnostic Medicine criteria (England et al. 2005). CONCLUSION: The frequency of polyneuropathy was significantly higher in PD patients than in controls (45% versus 2%, p<0.0001). We did not establish a relationship in the PD group according to long-term L-DOPA usage, PD duration, or age. It should be assumed that a neurodegenerative process underlies the involvement of the central and peripheral nervous systems in PD patients.

• MeSH
• dospělí MeSH
• elektromyografie MeSH
• komorbidita * MeSH
• levodopa aplikace a dávkování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nemoci periferního nervového systému diagnóza   epidemiologie   MeSH
• Parkinsonova nemoc farmakoterapie   epidemiologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• věkové faktory MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• levodopa MeSH

The development of painful paclitaxel-induced peripheral neuropathy (PIPN) represents a major dose-limiting side effect of paclitaxel chemotherapy. Here we report a promising effect of duvelisib (Copiktra), a novel FDA-approved PI3Kδ/γ isoform-specific inhibitor, in preventing paclitaxel-induced pain-like behavior and pronociceptive signaling in DRGs and spinal cord dorsal horn (SCDH) in rat and mouse model of PIPN. Duvelisib blocked the development of mechanical hyperalgesia in both males and females. Moreover, duvelisib prevented paclitaxel-induced sensitization of TRPV1 receptors, and increased PI3K/Akt signaling in small-diameter DRG neurons and an increase of CD68+ cells within DRGs. Specific optogenetic stimulation of inhibitory neurons combined with patch-clamp recording revealed that duvelisib inhibited paclitaxel-induced weakening of inhibitory, mainly glycinergic control on SCDH excitatory neurons. Enhanced excitatory and reduced inhibitory neurotransmission in the SCDH following PIPN was also alleviated by duvelisib application. In summary, duvelisib showed a promising ability to prevent neuropathic pain in PIPN. The potential use of our findings in human medicine may be augmented by the fact that duvelisib is an FDA-approved drug with known side effects.SIGNIFICANCE STATEMENT We show that duvelisib, a novel FDA-approved PI3Kδ/γ isoform-specific inhibitor, prevents the development of paclitaxel-induced pain-like behavior in males and females and prevents pronociceptive signaling in DRGs and spinal cord dorsal horn in rat and mouse model of paclitaxel-induced peripheral neuropathy.

• Klíčová slova
• PI3K, TRPV1, dorsal horn, glycine, neuropathy, pain,
• MeSH
• bolest MeSH
• fosfatidylinositol-3-kinasy MeSH
• fytogenní protinádorové látky * farmakologie   MeSH
• hyperalgezie chemicky indukované   farmakoterapie   prevence a kontrola   MeSH
• isochinoliny MeSH
• krysa rodu Rattus MeSH
• myši MeSH
• nemoci periferního nervového systému MeSH
• neuralgie * chemicky indukované   farmakoterapie   prevence a kontrola   MeSH
• paclitaxel škodlivé účinky   MeSH
• puriny MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• duvelisib MeSH Prohlížeč
• fytogenní protinádorové látky * MeSH
• isochinoliny MeSH
• paclitaxel MeSH
• puriny MeSH

• Klíčová slova
• ELECTROMYOGRAPHY *, NEURONS/physiology *, PERIPHERAL NERVES/physiology *, SPASMOPHILIA/physiology *,
• MeSH
• elektromyografie * MeSH
• lidé MeSH
• motorické neurony * MeSH
• nemoci periferního nervového systému * MeSH
• neurony fyziologie   MeSH
• periferní nervy fyziologie   MeSH
• tetanie fyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Homocysteinemia is a metabolic condition characterized by abnormally high level of homocysteine in the blood and is considered to be a risk factor for peripheral neuropathy. However, the cellular mechanisms underlying toxic effects of homocysteine on the processing of peripheral nociception have not yet been investigated comprehensively. Here, using a rodent model of experimental homocysteinemia, we report the causal association between homocysteine and the development of mechanical allodynia. Homocysteinemia-induced mechanical allodynia was reversed on pharmacological inhibition of T-type calcium channels. In addition, our in vitro studies indicate that homocysteine enhances recombinant T-type calcium currents by promoting the recycling of Cav3.2 channels back to the plasma membrane through a protein kinase C-dependent signaling pathway that requires the direct phosphorylation of Cav3.2 at specific loci. Altogether, these results reveal an unrecognized signaling pathway that modulates the expression of T-type calcium channels, and may potentially contribute to the development of peripheral neuropathy associated with homocysteinemia.

• MeSH
• buněčná membrána metabolismus   MeSH
• homocystein krev   MeSH
• hyperalgezie etiologie   metabolismus   MeSH
• hyperhomocysteinemie komplikace   MeSH
• krysa rodu Rattus MeSH
• modely nemocí na zvířatech MeSH
• nemoci periferního nervového systému etiologie   metabolismus   MeSH
• nocicepce fyziologie   MeSH
• potkani Wistar MeSH
• spinální ganglia metabolismus   MeSH
• vápník metabolismus   MeSH
• vápníkové kanály - typ T metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• homocystein MeSH
• vápník MeSH
• vápníkové kanály - typ T MeSH

The aim of review is to give basic information on the method of peripheral neuropathy examination using biothesiometry technique. Impaired vibratory threshold can be identified in all patients with peripheral neuropathies, the diabetic, uremic, alcoholic or paraneoplastic ones. It is a simple, sensitive and comfortable method for daily screening. On the other hand it is sufficiently sensitive for detection and evaluation of peripheral neuropathy. Principle is a vibrating probe, vibration amplitude can be changed by voltage adjustment. Biothesiometry is used in diagnostics of peripheral neuropathies with impaired vibratory perception threshold, mainly in diabetology and neurology.

• MeSH
• diabetické neuropatie diagnóza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nemoci periferního nervového systému diagnóza   MeSH
• neurologické vyšetření přístrojové vybavení   MeSH
• senzorické prahy MeSH
• vibrace * MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH

INTRODUCTION: Electrophysiological diagnosis of cardiac autonomic neuropathy (CAN) is based on the evaluation of cardiovascular autonomic reflex tests (CARTs). CARTs are relatively time consuming and must be performed under standardized conditions. This study aimed to determine whether thermal quantitative sensory testing (TQST) can be used as a screening tool to identify patients with diabetes at a higher risk of CAN. METHODS: Eighty-five patients with diabetes and 49 healthy controls were included in the study. Neurological examination, CARTs, TQST, biochemical analyses, and neuropathy symptom questionnaires were performed. RESULTS: CAN was diagnosed in 46 patients with diabetes (54%). CAN-positive patients with diabetes had significantly higher warm detection thresholds (WDT) and significantly lower cold detection thresholds (CDT) in all tested regions (thenar, tibia, and the dorsum of the foot). CDT on the dorsum < 21.8°C in combination with CDT on the tibia < 23.15°C showed the best diagnostic ability in CAN prediction, with 97.4 % specificity, 60.9% sensitivity, 96.6% positive predictive value, and 67.3% negative predictive value. CONCLUSION: TQST can be used as a screening tool for CAN before CART.

• Klíčová slova
• autonomic nervous system, diabetic neuropathy, small fiber neuropathy,
• MeSH
• autonomní nervový systém MeSH
• diabetes mellitus * MeSH
• diabetické neuropatie * diagnóza   MeSH
• lidé MeSH
• nemoci nervového systému * MeSH
• nemoci periferního nervového systému * diagnóza   MeSH
• senzorické prahy fyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Inherited peripheral neuropathies are a genetically heterogeneous group of disorders characterized by distal muscle weakness and sensory loss. Mutations in genes encoding aminoacyl-tRNA synthetases have been implicated in peripheral neuropathies, suggesting that these tRNA charging enzymes are uniquely important for the peripheral nerve. Recently, a mutation in histidyl-tRNA synthetase (HARS) was identified in a single patient with a late-onset, sensory-predominant peripheral neuropathy; however, the genetic evidence was lacking, making the significance of the finding unclear. Here, we present clinical, genetic, and functional data that implicate HARS mutations in inherited peripheral neuropathies. The associated phenotypic spectrum is broad and encompasses axonal and demyelinating motor and sensory neuropathies, including four young patients presenting with pure motor axonal neuropathy. Genome-wide linkage studies in combination with whole-exome and conventional sequencing revealed four distinct and previously unreported heterozygous HARS mutations segregating with autosomal dominant peripheral neuropathy in four unrelated families (p.Thr132Ile, p.Pro134His, p.Asp175Glu and p.Asp364Tyr). All mutations cause a loss of function in yeast complementation assays, and p.Asp364Tyr is dominantly neurotoxic in a Caenorhabditis elegans model. This study demonstrates the role of HARS mutations in peripheral neuropathy and expands the genetic and clinical spectrum of aminoacyl-tRNA synthetase-related human disease.

• Klíčová slova
• RNA processing, hereditary motor and sensory neuropathies, molecular genetics, neurodegeneration, whole-exome sequencing,
• MeSH
• Charcotova-Marieova-Toothova nemoc genetika   MeSH
• dědičné senzorické a autonomní neuropatie genetika   MeSH
• genetická vazba genetika   MeSH
• histidin-tRNA-ligasa genetika   MeSH
• lidé MeSH
• mutace genetika   MeSH
• nemoci periferního nervového systému genetika   MeSH
• rodokmen MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• histidin-tRNA-ligasa MeSH

OBJECTIVES: To confirm the changes in the results of EMG assessment of lower-limb peripheral nerves in patients treated with statins in the longer follow-up period of 3 years. BACKGROUND: Long-term treatment with statins may have adverse effects: affection of muscles or peripheral nervous system. The frequency of affection of the peripheral nervous system has not been thoroughly investigated; our previous study showed the signs of peripheral nerve damage in the results of EMG assessment. DESIGN/METHODS: Forty-two patients (23 males, 19 females, mean age 51.9 and 52.3 years) with a definitive diagnosis of combined hyperlipidemia were studied. Other metabolic disorders or chronic ethanol abuse were excluded. Initial examinations included laboratory and neurophysiological measures (peroneal and tibial nerves: MNCV, CMAP, F-wave mean latency; superficial peroneal and sural nerve: SNCV, SNAP). Subsequently, treatment with simvastatin 20 mg daily was initiated. Patients were followed for 36 months with repeated neurophysiological examinations on 24 and 36 months after statin treatment initiation. RESULTS: None of the patients reported subjective symptoms typical for peripheral neuropathy. Neurophysiological examination of lower-limb peripheral nerves demonstrated statistically significant prolongation of F-wave mean latency on peroneal and tibial nerves (p<0.0001, paired t-test). CONCLUSIONS: The study confirmed that long-term treatment with statins caused a clinically silent but still definite damage to peripheral nerves when the treatment lasts longer than 2 years.

• MeSH
• časové faktory MeSH
• dospělí MeSH
• elektromyografie MeSH
• hyperlipidemie farmakoterapie   epidemiologie   MeSH
• incidence MeSH
• lidé středního věku MeSH
• lidé MeSH
• následné studie MeSH
• nemoci periferního nervového systému chemicky indukované   epidemiologie   patofyziologie   MeSH
• nervus peroneus patofyziologie   MeSH
• nervus tibialis patofyziologie   MeSH
• prospektivní studie MeSH
• statiny aplikace a dávkování   škodlivé účinky   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• Názvy látek
• statiny MeSH