[Vestibular rehabilitation for peripheral vestibular hypofunction: an interdisciplinary consensus]. / Vestibulyarnaya reabilitatsiya pri perifericheskoi vestibulyarnoi gipofunktsii: mezhdistsiplinarnyi konsensus.

The literature review presents approaches to the management of patients with vestibular disorders. The principles of organization of vestibular rehabilitation in peripheral vestibular hypofunction, indications for appointment, factors influencing its implementation, technique, methods of evaluating effectiveness are considered in detail. Attention is drawn to the fact that the selection of exercises and the duration of vestibular rehabilitation is carried out individually and depends on many factors, including the nature of vestibular deficiency and the specific characteristics of the patient. The possibilities of using additional pharmacological therapy with histamine preparations, which can accelerate the onset of vestibular compensation, are shown. It is noted that vestibular rehabilitation is a safe and effective method of treating peripheral vestibular hypofunction and should be recommended to patients of all ages with vestibular disorders leading to limited social and physical activity.

Pharmacotherapy of cerebellar and vestibular disorders.

PURPOSE OF REVIEW: Major therapeutic advances have been made in patients with episodic and progressive cerebellar ataxias, downbeat nystagmus and some vestibular disorders. We provide an update review on this subject highlighting important research findings from the last two years. RECENT FINDINGS: Recently, the use of omaveloxolone for 2 years significantly improved upright stability in Friedreich's ataxia patients. In an open-label study, N-acetyl-l-leucine administered for 6-weeks significantly improved clinical impression of change, ataxia, and quality of life in patients with Niemann-Pick disease type C1. A 12-week treatment with dalfampridine was associated with improved standing balance in a subgroup of patients with multiple sclerosis. A gluten-free diet alone improved ataxia in half of patients with antiglutamic acid decarboxylase (GAD) ataxia, suggesting that gluten sensitivity might be part of the underlying pathogenesis in anti-GAD ataxia. In a head-to-head trial, both prolonged-release 4-aminopyridine (4-AP) and acetazolamide effectively reduced the attacks up to 60% in patients with episodic ataxia type 2 (EA2), albeit 4-AP had fewer adverse effects. Small observational studies have shown that patients with episodic vestibular syndrome who cannot be diagnosed as definite or probable vestibular migraine, might still improve vestibular symptoms following preventive treatment for migraine. The use of vitamin D supplementation in benign paroxysmal positional vertigo, steroids in acute unilateral vestibulopathy, and betahistine in Ménière's disease patients remains controversial. SUMMARY: Although the use of several therapies is being established in the treatment of cerebellar and vestibular disorders, there is an urgent need for prospective controlled therapeutic trials.

Therapeutic effect of steroids on vestibular neuritis: Systematic review and meta-analysis.

OBJECTIVES: The present meta-analysis sought to assess further evidence for the efficacy of steroids in vestibular neuritis (VN). METHODS: The PubMed, EMBASE and Cochrane Library databases were searched through 30 August 2019. The main outcome measure was dizziness handicap inventory (DHI) and secondary outcomes included complete caloric recovery and improvement of canal paresis (CP). The follow-up times were divided into short, mid and long-term. RESULTS: Among 276 records identified, 5 studies (n = 253) were included in the analysis. The therapeutic effect of steroid on VN was confirmed (Hedges' g = 0.172, 95% CI 0.05-0.30, p = .006). Although there was no significant difference between steroids and control in the DHI score (Hedges' g = -0.323, 95% CI -0.533 to -0.113, p < .01), significant effect was seen on complete caloric recovery and improvement in CP (Hedges' g = 0.364, 95% CI 0.18-0.55, p < .0001; Hedges' g = 0.592, 95% CI 0.32-0.59, p < .0001). CONCLUSIONS: The results suggest that corticosteroids have an effect on the results of caloric tests for VN recovery, especially in long-term follow-up. However, in terms of dizziness handicap, we did not find any evidence of positive effect on corticosteroid. More data are required before recommendations can be made regarding management in patients on corticosteroids.

Hair cell uptake of gentamicin in the developing mouse utricle.

Intratympanic injection of gentamicin has proven to be an effective therapy for intractable vestibular dysfunction. However, most studies to date have focused on the cochlea, so little is known about the distribution and uptake of gentamicin by the counterpart of the auditory system, specifically vestibular hair cells (HCs). Here, with a combination of in vivo and in vitro approaches, we used a gentamicin-Texas Red (GTTR) conjugate to investigate the mechanisms of gentamicin vestibulotoxicity in the developing mammalian utricular HCs. In vivo, GTTR fluorescence was concentrated in the apical cytoplasm and the cellular membrane of neonatal utricular HCs, but scarce in the nucleus of HCs and supporting cells. Quantitative analysis showed the GTTR uptake by striolar HCs was significantly higher than that in the extrastriola. In addition, the GTTR fluorescence intensity in the striola was increased gradually from 1 to 8 days, peaking at 8-9 days postnatally. In vitro, utricle explants were incubated with GTTR and candidate uptake conduits, including mechanotransduction (MET) channels and endocytosis in the HC, were inhibited separately. GTTR uptake by HCs could be inhibited by quinine, a blocker of MET channels, under both normal and stressed conditions. Meanwhile, endocytic inhibition only reduced GTTR uptake in the CoCl2 hypoxia model. In sum, the maturation of MET channels mediated uptake of GTTR into vestibular HCs. Under stressed conditions, MET channels play a pronounced role, manifested by channel-dependent stress enhanced GTTR permeation, while endocytosis participates in GTTR entry in a more selective manner.

The use of ondansetron for the treatment of nausea in dogs with vestibular syndrome.

BACKGROUND: Vestibular syndrome is often accompanied by nausea. Drugs currently approved for its treatment have been developed to stop vomiting but not nausea. The efficacy of 5-HT3 receptor antagonists to reduce nausea has been described for chemotherapy, but not for nausea secondary to vestibular disorders. METHODS: Sixteen dogs with vestibular syndrome-associated nausea were included in the open-label, multicentre study. The intensity of nausea-like behaviour was analysed before ondansetron administration (0.5 mg/kg i.v.) and 2 h afterwards, using a validated 5-point-scale. The occurrence and frequency of salivation, lip licking, restlessness, vocalisation, lethargy, and vomiting were assessed. RESULTS: All dogs initially showed signs of nausea, whereas only 31% showed vomitus. The intensity of nausea was significantly reduced in all dogs (p ≤ 0.0001) 2 h after ondansetron administration, including the clinical signs of nausea analysed in 11 dogs (salivation [p = 0.0078], lip licking [p = 0.0078], restlessness [p = 0.0039], and lethargy [p = 0.0078]) except for vocalisation (p > 0.9999). CONCLUSIONS: The results provide preliminary evidence of the potential benefit of ondansetron in the treatment of nausea, which was present in all examined dogs. Vomiting was only observed in 5 dogs indicating that nausea can occur separately and should not be perceived only as a preceding stimulation of the vomiting centre.

Factors implicated in response to treatment/prognosis of vestibular migraine.

PURPOSE: To identify patient factors that influence response to therapy in patients with vestibular migraines. METHODS: A retrospective cohort study was performed at a university-based tertiary medical center. PATIENTS: 47 patients evaluated for treatment of definite vestibular migraine, per the Barany Society criteria, from 2015 to 2019. INTERVENTIONS: A protocol of antidepressants, antiepileptics, beta blockers, and vestibular rehabilitation. Patients failing initial therapy received botulinum toxin per the PREEMPT protocol. Vestibular rehabilitation for motion desensitization in case of known vestibular dysfunction. OUTCOME MEASURES: Quality of life measured per the dizziness handicap inventory (DHI). Pre- and post-treatment DHI scores (total and domain scores) and change in DHI were correlated against patient-specific variables to determine factors associated with change in response to therapy. Patient factors included demographic variables, medical comorbidities, comorbid otologic or pain symptoms, treatment modality, and initial DHI scores. RESULTS: 47 patients underwent therapy for vestibular migraine. This population had a significant DHI reduction of 17.3 ± 25.2 (p < 0.001) with therapy. Univariate analysis showed that female gender, comorbid benign paroxysmal positional vertigo, and high initial DHI were significantly associated with greater reduction in DHI scores (ß = - 7.92, p = 0.033; ß = - 18.65, p = 0.028; ß = - 0.458, p = 0.016, respectively). Conversely, cervicalgia and oscillopsia were significantly associated with a lower reduction in DHI scores (ß = 5.525, p = 0.024 and ß = 21.48, p = 0.027, respectively). CONCLUSIONS: Vestibular migraine is a complex disorder with heterogeneous response to therapy. This study shows that patient-specific factors of gender, cervicalgia, oscillopsia, BPPV, and high DHI scores on presentation may influence response to common vestibular migraine therapy.

[Betahistine in vestibular disorders: current concepts and perspectives]. / Sovremennye predstavleniya o roli betagistina v lechenii zabolevanii vestibulyarnoi sistemy.

The goal of this paper is to review the pharmacological profile of betahistine and evidence for using it in the treatment of common vestibular disorders. Betahistine is a weak agonist for histamine H1 receptors and strong antagonist for histamine H3 receptors. It demonstrates the maximum benefit in different types of peripheral vertigo, especially in Meniere's disease. The best results in decreasing intensity of vertigo, frequency of attacks and stimulation of vestibular compensation were obtained in daily dose 48 mg during 3 months. In benign paroxysmal positional vertigo betahistine is used to treat residual dizziness after successful treatment of otolithiasis and to reduce the severity of vertigo during repositioning maneuvers. In vestibular neuritis betahistine stimulates central compensation during vestibular rehabilitation. A new once-daily drug formulation of modified-release betahistine is non-inferior to traditional and has a comparable safety profile, and could improve patient adherence. The implication of betahistine in the treatment of central vestibular disorders is under-researched. The efficacy of betahistine in increasing of vestibular compensation in post-stroke central vestibular disorders, persistent postural-perceptual dizziness and its role in vestibular migraine need further investigation.

Histamine H1 Receptor Contributes to Vestibular Compensation.

Vestibular compensation is responsible for the spontaneous recovery of postural, locomotor, and oculomotor dysfunctions in patients with peripheral vestibular lesion or posterior circulation stroke. Mechanism investigation of vestibular compensation is of great importance in both facilitating recovery of vestibular function and understanding the postlesion functional plasticity in the adult CNS. Here, we report that postsynaptic histamine H1 receptor contributes greatly to facilitating vestibular compensation. The expression of H1 receptor is restrictedly increased in the ipsilesional rather than contralesional GABAergic projection neurons in the medial vestibular nucleus (MVN), one of the most important centers for vestibular compensation, in unilateral labyrinthectomized male rats. Furthermore, H1 receptor mediates an asymmetric excitation of the commissural GABAergic but not glutamatergic neurons in the ipsilesional MVN, which may help to rebalance bilateral vestibular systems and promote vestibular compensation. Selective blockage of H1 receptor in the MVN significantly retards the recovery of both static and dynamic vestibular symptoms following unilateral labyrinthectomy, and remarkably attenuates the facilitation of betahistine, whose effect has traditionally been attributed to its antagonistic action on the presynaptic H3 receptor, on vestibular compensation. These results reveal a previously unknown role for histamine H1 receptor in vestibular compensation and amelioration of vestibular motor deficits, as well as an involvement of H1 receptor in potential therapeutic effects of betahistine. The findings provide not only a new insight into the postlesion neuronal circuit plasticity and functional recovery in the CNS, but also a novel potential therapeutic target for vestibular disorders.SIGNIFICANCE STATEMENT Vestibular disorders manifest postural imbalance, nystagmus, and vertigo. Vestibular compensation is critical for facilitating recovery from vestibular disorders, and of great importance in understanding the postlesion functional plasticity in the adult CNS. Here, we show that postsynaptic H1 receptor in the medial vestibular nucleus (MVN) contributes greatly to the recovery of both static and dynamic symptoms following unilateral vestibular lesion. H1 receptor selectively mediates the asymmetric activation of commissural inhibitory system in the ipsilesional MVN and actively promotes vestibular compensation. The findings provide not only a new insight into the postlesion neuronal circuit plasticity and functional recovery of CNS, but also a novel potential therapeutic target for promoting vestibular compensation and ameliorating vestibular disorders.

Autoimmune Vestibulocerebellar Syndromes.

Autoimmune disorders affecting the vestibular end organs, vestibular pathways, vestibular nuclei, and vestibulocerebellum are often underrecognized as a cause of chronic dizziness and ataxia. Autoantibodies specific for cell-surface, synaptic, and intracellular neural antigens serve as biomarkers of these disorders. This article describes the epidemiology, clinical presentation, diagnostic considerations, imaging findings, treatment, and prognosis of autoimmune disorders, in which the vestibulocerebellar syndrome is the main or presenting clinical presentation. Antibodies specific for intracellular antigenic targets described in the article are PCA-1 (Purkinje cell cytoplasmic antibody type 1, also known as anti-Yo), ANNA-1 (antinuclear neuronal antibody type 1, also known as anti-Hu), ANNA-2 (antinuclear neuronal antibody type 2, also known as anti-Ri), Ma1/2 (anti-Kelch-like 11/12 antibody), Kelch-like 11, amphiphysin, CV2 (collapsin response 2, also known as collapsin response mediator protein-5 [CRMP5]), VGCC (voltage-gated calcium channel), GAD65 (glutamic acid decarboxylase 65-kDa isoform), AP3B2 (adaptor protein 3B2, also known as anti-Nb), MAP1B (microtubule-associated protein 1B antibody, also known as anti-PCA-2), and neurochondrin antibodies. Antibodies targeting cell-surface or synaptic antigenic targets described in the article include DNER (delta/notchlike epidermal growth factor related receptor; antigen to anti-Tr), CASPR2 (contactin-associated proteinlike 2), septin-5, Homer-3, and mGluR1 (metabotropic glutamate receptor 1). The vestibulocerebellar presentation is largely indistinguishable among these conditions and is characterized by subacute onset of cerebellar symptoms over weeks to months. The diagnosis of autoimmune vestibulocerebellar syndromes is based on a combination of clinical and serological features, with a limited role for neuroimaging. Subtle eye movement abnormalities can be an early feature in many of these disorders, and therefore a meticulous vestibulo-ocular examination is essential for early and correct identification. Cancer occurrence and its type are variable and depend on the autoantibody detected and other cancer risk factors. Treatment comprises immunotherapy and cancer-directed therapy. Acute immunotherapies such as intravenous immunoglobulin, plasma exchange, and steroids are used in the initial phase, and the use of long-term immunosuppression such as rituximab may be necessary in relapsing cases. Outcomes are better if immunotherapy is started early. The neurologic prognosis depends on multiple factors.

Analysis of the effectiveness of the prophylaxis of vestibular migraine depending on the diagnostic category and the prescribed drug.

INTRODUCTION: Vestibular migraine (VM) consists of recurrent episodes of vestibular symptoms that are accompanied by migraine in at least 50% of the episodes. The criteria of the Bárány Society include two diagnostic categories: "actual" vestibular migraine and probable vestibular migraine. There is a wide range of drugs that can be prescribed for the prophylactic treatment of VM, but recommendations for the selection of the most appropriate drug are currently lacking. OBJECTIVE: To measure the extent to which the prophylactic treatment of VM reduces vestibular symptoms, headache and the number of crises depending on the diagnostic category of the Bárány Society and the drug used for prophylaxis. MATERIAL AND METHODS: This is a multicenter prospective study. Patients with VM who presented to any of the participating centers and who subsequently met the VM criteria were prescribed one of the following types of prophylaxis: acetazolamide, amitriptyline, flunarizine, propranolol or topiramate. Patients were called back for a follow-up visit 5 weeks later. This allowed the intensity of vestibular symptoms, headache and the number of crises before and during treatment to be compared. RESULTS: 31 Patients met the inclusion criteria. During the treatment, all the measured variables decreased significantly. In a visual analogue scale, the intensity of vestibular symptoms decreased by 45.8 points, the intensity of headache decreased by 47.8 points and patients suffered from 15.6 less monthly crises compared to the period before the treatment. No significant between-group differences were found when patients were divided based on their diagnostic category or the choice of prophylaxis prescribed to them. CONCLUSION: The treatment of VM produces a reduction of symptoms and crises with no significant differences based on patients' diagnostic categories or the choice of prophylaxis prescribed to them.

[Syncope, pain in the large joints, and painful swelling of the right eye in a 51-year-old patient : Pitfalls in the diagnosis and treatment of a rare disease]. / Synkope, Schmerzen der großen Gelenke und schmerzhafte Rötung des rechten Auges bei einer 51-jährigen Patientin : Fallstricke in Diagnostik und Therapie einer seltenen Erkrankung.

In the present case we report on a 51-year-old patient diagnosed with Cogan syndrome. This vasculitis of variable vessel size is a rare disease that poses a major challenge for the correct diagnostics and therapy. In the classic setting, it comprises a triad of non-syphilitic interstitial keratitis as well as hearing loss with vestibular dysfunction. A vascultis-related aortitis, an uncertain, more likely degenerative structure in combination with strongly elevated inflammation parameters was misinterpreted as infective endocarditis for a long time and treated with anti-infective medications. After diagnosis the patient recovered following treatment with high-dose steroids and in the further course cyclophosphamide and tumor necrosis factor­α blockers.

Hypermobility in individuals with Kabuki syndrome: The effect of growth hormone treatment.

Kabuki syndrome (KS) is a multiple congenital malformation syndrome which has been described across all ethnic groups. Most KS patients possess two genetic subtypes: KMT2D-associated, autosomal-dominant KS type 1 (KS1; OMIM 147920); and KDM6A-associated, X-linked-dominant KS type 2. Generalized joint hypermobility is one feature of KS, but its exact incidence and pattern is not well described in the literature. As part of our prospective study on the metabolic and growth effect of GH treatment, we assessed children from our Dutch Kabuki cohort who were eligible for growth hormone therapy. We assessed severity and pattern of joint hypermobility, both before and after 24 months of growth hormone replacement therapy. The prevalence of hypermobility was 31% in boys and 14% in girls using the Beighton score and 69% in boys and 57% in girls using the Bulbena score. This varies from the general population where girls are more affected. After 2 years of growth hormone treatment, there was a statistically significant decrease in the presence of joint hypermobility to 6% using the Bulbena score and none with respect to the Beighton score. We hypothesized that this result suggests a direct effect of growth hormone on connective tissue in patients with KS.

Vestibular migraine treatment and prevention.

Vestibular migraine probably represents the second most common cause of vertigo after benign positional vertigo, by far exceeding Ménière disease. There are still relatively few published reports on vestibular migraine management, despite its enormous importance in daily practice. In 2003 the first clinical definition of vestibular migraine was proposed. Studies published before 2003 used variable terms for vestibular migraine. Some authors recommend treating vestibular migraine using multiple drugs; others have focused on using only one drug. Although at present it is not possible to quantify the effects of the treatments proposed, some recommendations can be made.

[Pharmacotherapy of Vestibular Disorders, Nystagmus and Cerebellar Disorders]. / Medikamentöse Therapiemöglichkeiten bei vestibulären Störungen, Nystagmus und zerebellären Ataxien.

There are currently different groups of drugs for the pharmacotherapy of vertigo, nystagmus and cerebellar disorders: antiemetics; anti-inflammatories, antimenieres, and antimigraineous medications and antidepressants, anticonvulsants, aminopyridines as well as acetyl-DL-leucine. In acute unilateral vestibulopathy, corticosteroids improve the recovery of peripheral vestibular function, but currently there is not sufficient evidence for a general recommendation. There is insufficient evidence to support the view that 16 mg t. i. d. or 48 mg t. i. d. betahistine has an effect in Menière's disease. Therefore, higher dosages are recommended. In animal studies, it was shown that betahistine increases cochlear blood flow. In vestibular paroxysmia, oxcarbazepine was effective (one randomized controlled trial (RCT)). Aminopyridines are recommended for the treatment of downbeat nystagmus (two RCTs) and episodic ataxia type 2 (EA2, one RCT). There has been no RCT on the efficacy of beta-blockers or topiramate but one RCT on flunarizine in vestibular migraine. Based on clinical experience, a treatment analogous to that for migraine without aura can be recommended. Acetyl-DL-leucine improved cerebellar ataxia (two observational studies); it also accelerated central compensation in an animal model of acute unilateral lesion, but RCTs were negative. There are ongoing RCTs on treatment of vestibular paroxysmia with carbamazepine (VESPA), acute unilateral vestibulopathy with betahistine (BETAVEST), vestibular migraine with metoprolol (PROVEMIG), benign paroxysmal positional vertigo with vitamin D (VitD@BPPV), EA2 with 4-aminopyridine versus acetazolamide (EAT-2-TREAT), and cerebellar ataxias with acetyl-DL-leucine (ALCAT).

The Spectrum of Vestibular and Ocular Motor Abnormalities in Thiamine Deficiency.

PURPOSE: The first aim of this review is to summarize recent ocular motor signs in pre-encephalopathy patients with nutritional deficiency at risk of thiamine deficiency. Timely recognition of thiamine depletion in these patients, who may have a normal brain MRI, could lead to appropriate management and prevention of Wernicke's encephalopathy (WE) with full recovery. The second aim is to incorporate recent diagnostic testing on the revised WE diagnostic criteria and the identification of patients who may show slow, partial, or no response to treatment. RECENT FINDINGS: Selective vulnerability of periventricular gray neurons in thiamine deficiency is well known. Involvement of the vestibular and abducens nuclei may precede encephalopathy. Studies have shown mild ophthalmoparesis and bilateral symmetric vestibular loss in thiamine deficiency. Moreover, quantitative data has shown decreased horizontal vestibulo-ocular reflex (VOR) gain and nystagmus, with a favorable response to timely treatment. Ophthalmoparesis, horizontal nystagmus, and decreased gain of the horizontal VOR, sparing the vertical VOR, may be present in the early pre-encephalopathy stage of thiamine deficiency. Rapid response to a loading dose of parenteral thiamine might be seen in some cases and normalization, albeit slower in others. In contrast, analogous to the Korsakoff's syndrome, ocular motor and vestibular abnormalities may show only partial improvement. Future studies in larger populations at risk are needed to confirm the results of these preliminary observations.

[The influence of Memoplant monotherapy on the dizziness]. / Vliianie preparata Memoplant v rezhime monoterapii na golovokruzhenie.

The objective of the present work was to study the influence of the dry extract from the leaves of Ginkgo biloba EGb 761 (used as monotherapy at a dose of 120 mg twice daily during 4 months) on the vestibular function of the patients presenting with cochleovestibular pathology of peripheral and mixed genesis. We present the results obtained by the objective and subjective methods for the evaluation of the vestibular function as well as the neurological and psychoemotional state of the 40 patients that was carried out during the four months of memoplant monotherapy. It is concluded that monotherapy with the use of the dry extract from Ginkgo biloba leaves can be applied for the purpose of improvement of static and dynamic balancing state. Moreover, this memoplant preparation can be used as a means of prophylaxis of recurrent dizziness that in addition reduces the severity of anxiety and depression without producing adverse side effects.

Paradoxical vestibular syndrome in a dog from western Newfoundland infected with French heartworm (Angiostrongylus vasorum).

A dog from western Newfoundland was presented with paradoxical vestibular syndrome. First-stage larvae of Angiostrongylus vasorum were detected on fecal examination. Treatment with milbemycin oxime resulted in resolution of signs. This is the first report of the spread of this parasite to western Newfoundland and of paradoxical vestibular syndrome in a dog infected with A. vasorum.

Syndrome vestibulaire paradoxal chez un chien de l'ouest de Terre-Neuve infecté par des vers du cœur(Angiostrongylus vasorum). Un chien de l'ouest de Terre-Neuve a été présenté avec un syndrome vestibulaire paradoxal. Des larves de premier stade d'Angiostrongylus vasorum ont été détectées à l'examen fécal. Le traitement à l'aide d'oxime de milbémycine a produit une disparition des symptômes. Il s'agit du premier rapport de la propagation de ce parasite dans l'ouest de Terre-Neuve et du syndrome vestibulaire paradoxal chez un chien infecté par A. vasorum.(Traduit par Isabelle Vallières).

Fixed combination of cinnarizine and dimenhydrinate in the prophylactic therapy of vestibular migraine: an observational study.

Vestibular migraine (VM) is one of the most frequent causes of episodic vertigo, with a lifetime prevalence of 0.98%. Prophylactic therapy includes calcium channel blockers, beta-blockers, antiepileptic drugs and antidepressants. We studied the association of cinnarizine 20 mg and dimenhydrinate 40 mg (Arlevertan) in a group of 22 patients affected by definite VM. Proposed therapy included one tablet twice a day for 1 month, which was repeated three times with 1 month of interval between drug intake; results were compared with those of a control group of 11 VM patients who asked to observe only lifestyle measures for migraine. The main outcome was the number of vertigo and headache crises in the 6 months before therapy and in the 6 months of follow-up. Subjects performing Arlevertan presented during the 6 months of therapy a decrease of vertigo attacks from 5.3 to 2.1 and of headaches from 4.3 to 1.7 (p < 0.0001); 68% of these subjects reported a decrease of at least 50% of vertigo attacks, while 63% of headaches. Conversely, vertigo attacks decreased from 3.5 to 2.2 and headaches from 2.6 to 2 in patients observing only lifestyle; 18% of these subjects reported a decrease of at least 50% of vertigo crises and 27% of headaches. Our data do not differ from those of previous works assessing efficacy of different prophylactic therapies for VM and reporting consistent reduction of vertigo spells in a rate of patients ranging from 60 and 80%.

Neonatal case of novel KMT2D mutation in Kabuki syndrome with severe hypoglycemia.

A newborn Japanese girl with Kabuki syndrome had neonatal persistent hyperinsulinemic hypoglycemia, which seemed to be a rare complication of Kabuki syndrome. On sequence analysis she was found to have a novel heterozygous KMT2D mutation. Diazoxide therapy was effective for the hypoglycemia. Hypoglycemia should be considered when Kabuki syndrome patients have convulsion or other non-specific symptoms. Diazoxide may help to improve hypoglycemia in patients with Kabuki syndrome complicated with hyperinsulinemic hypoglycemia.

Practical selection of antiemetics in the ambulatory setting.

Nausea and vomiting are mediated primarily by three neurotransmitter pathways: visceral stimulation releases dopamine and serotonin; vestibular and central nervous system activation release histamine and acetylcholine; and chemoreceptor trigger zone activation releases dopamine and serotonin. Clinicians can improve the effectiveness and cost-effectiveness of treatments by targeting the appropriate pathways. Antihistamines and anticholinergics are most effective in patients with vestibular-mediated nausea secondary to vertigo. Serotonin antagonists block serotonin in the intestines and chemoreceptor trigger zone, and are most effective for treating gastroenteritis. Dopamine antagonists block dopamine in the intestines and chemoreceptor trigger zone; indications for these agents are similar to those for serotonin antagonists. For treatment of mild pregnancy-induced nausea, pyridoxine with or without doxylamine is recommended, and ginger may also be effective. In patients with migraine headache-associated nausea, metoclopramide improves response to oral anti-migraine agents. Ondansetron reduces nausea and vomiting in children with acute gastroenteritis and in women with hyperemesis gravidarum.