Characteristic Clinical Sign Research Articles

‘BLUES’ procedure for assessing the blue level of the sclera in Osteogenesis Imperfecta

PurposeBlue sclera is a characteristic and common clinical sign of Osteogenesis Imperfecta (OI). However, there is currently no widely accepted, objective method for assessing and grading blue sclera in individuals with OI.To address this medical need, this study is aimed to design and validate a new method called ‘BLUES’ (BLUe Eye Sclera) to objectively identify and quantify the blue color in the sclera of patients affected by OI.MethodsSixty-two patients affected by OI and 35 healthy controls were enrolled in the present prospective study, for a total of 194 eyes analyzed.In the 'BLUES' procedure, eye images from patients with OI and control subjects were analyzed to assess and grade the blue level of the sclera using Adobe Photoshop Software. The validation process then involved comparing the results obtained with the ‘BLUES’ procedure to the judgement of experienced ophthalmologists (JEO).A receiver-operating characteristic (ROC) curve analysis was used to examine the overall discriminatory power. The sensitivity and specificity levels and the Cohen's Kappa (K) indexes of ‘BLUES’ and ‘JEO’ were estimated versus the standard OI diagnosis. The K indexes of ‘BLUES’ versus ‘JEO’ were also evaluated.ResultsThe optimal cut-off point of the scleral blue peak was calculated at 17%. Our findings demonstrated a sensitivity of 89% (CI95%: 0.835–0.945) and specificity of 87% (CI95%: 0.791–0.949) for the ‘BLUES’ procedure with an agreement versus the diagnosis of OI of 0.747. In comparison, the sensitivity and specificity of ‘JEO’ ranged from 89 to 94% and 77% to 100%, respectively, with an agreement ranging from 0.663 to 0.871 with the diagnosis of OI. The agreement between ‘BLUES ‘and ‘JEO’ evaluations ranged from 0.613 to 0.734.ConclusionsOur findings demonstrated an 89% sensitivity and an impressive 87% specificity of our method to analyze the blue sclera in OI. The results indicated high agreement with disease diagnosis and were consistent with evaluations by experienced ophthalmologists. The ‘BLUES’ procedure appears to be a simple, reliable and objective method for effectively identify and quantify the blue color of the sclera in OI.

Recommendations for the healthcare of patients with FOP

Fibrodysplasia ossificans progressiva (FOP) is avery rare, severe genetic disorder triggered by again-of-function mutation in the ACVR1 gene that codes for the typeI bone morphogenetic protein (BMP) receptor ACVR1 (activinAreceptor-type1), also known as ALK2 (activin receptor-like kinase-2). It leads to the onset and progression of heterotopic ossification (HO) in soft and connective tissue. HO is often preceded by episodes of soft tissue swelling or flare-ups. Flare-ups, characteristic of FOP, may be induced by trauma, infection, vaccination, or other medications, as well as surgical procedures or may occur spontaneously. As patients age, they develop severe mobility limitations due to progressive HO formation, including immobility, causing ashortened life expectancy. FOP's first characteristic clinical sign is the congenital malformation of one or both big toes with valgus axis deviation, which is present in almost all patients. To confirm the diagnosis, molecular genetic analysis of the ACVR1 gene is possible. This white paper aims to provide an overview of the necessary prerequisites and conditions for the care of patients with FOP and positively contribute to patients with FOP by improving the overall availability of knowledge. To achieve this, relevant aspects of the care of the very rare disease FOP are presented, from the initial diagnosis to the care in regular care based on the authors' knowledge (German FOP network) and the international FOP Treatment Guidelines. The recommendations presented here are addressed to all actors and decision-makers in the health care system and are also intended to inform patients and the public.

The diagnosis and treatment of contact lens-induced limbal stem cell deficiency

Objective: To analyze the clinical features and treatment outcomes of eyes with contact lens-induced limbal stem cell deficiency (CL-iLSCD). Methods: This cross-sectional study involved patients diagnosed with CL-iLSCD at the Eye, Ear, Nose & Throat Hospital of Fudan University between October 2018 and September 2022. A total of 17 patients (25 eyes) with a mean age of (36.4±6.9) years were enrolled. Among them, 14 were females (82.4%). Corneal and limbal abnormalities, especially the range of epitheliopathy, were observed under a slit lamp biomicroscope with fluorescein staining. Anterior segment optical coherence tomography and in vivo laser scanning confocal microscopy were performed to obtain the central corneal epithelial thickness, density of basal epithelial cells and corneal nerve fiber length. The clinical features of CL-iLSCD, along with their treatment outcomes and related risk factors, were analyzed. Results: All patients wore soft contact lenses, with an average daily wearing time of (10.5±2.5) hours and a median wearing duration of 10 (4 to 30) years. Ocular symptoms, including decreased vision, ocular discomfort or pain, redness, and photophobia, were present in 22 eyes (88.0%). The most characteristic clinical sign of CL-iLSCD was comb-or whorl-pattern late fluorescein staining under cobalt blue light, which was most commonly seen at the superior limbus (25/25, 100.0%). Additionally, reductions in central corneal epithelial thickness, basal cell density, and corneal nerve fiber length were observed. A comprehensive score was assigned to each eye based on clinical findings and in vivo imaging biomarkers. LSCD was mild, moderate, and severe in 5, 11, and 8 eyes, respectively. A history of misdiagnosis was found in 20 eyes (80.0%). After discontinuing the use of contact lenses and receiving medical treatment, significant improvement was observed in all eyes, with 13 eyes fully recovered. Conclusions: The symptoms and clinical signs of CL-iLSCD can be subtle at the early stage. Discontinuing contact lens wear and medication are effective to treat CL-iLSCD.

Senso-Immunologic Prospects for Complex Regional Pain Syndrome Treatment.

Complex regional pain syndrome (CRPS) is a chronic pain syndrome that occurs in tissue injuries as the result of surgery, trauma, or ischemia. The clinical features of this severely painful condition include redness and swelling of the affected skin. Intriguingly, it was recently suggested that transient receptor potential ankyrin 1 (TRPA1) is involved in chronic post-ischemia pain, a CRPS model. TRPA1 is a non-selective cation channel expressed in calcitonin gene-related peptide (CGRP)-positive primary nociceptors that becomes highly activated in ischemic conditions, leading to the generation of pain. In this review, we summarize the history of TRPA1 and its involvement in pain sensation, inflammation, and CRPS. Furthermore, bone atrophy is also thought to be a characteristic clinical sign of CRPS. The altered bone microstructure of CRPS patients is thought to be caused by aggravated bone resorption via enhanced osteoclast differentiation and activation. Although TRPA1 could be a target for pain treatment in CRPS patients, we also discuss the paradoxical situation in this review. Nociceptor activation decreases the risk of bone destruction via CGRP secretion from free nerve endings. Thus, TRPA1 inhibition could cause severe bone atrophy. However, the suitable therapeutic strategy is controversial because the pathologic mechanisms of bone atrophy in CRPS are unclear. Therefore, we propose focusing on the remission of abnormal bone turnover observed in CRPS using a recently developed concept: senso-immunology.

Sarcoma de Kaposi na Odontologia: Um levantamento epidemiológico no Brasil.

HIV-AIDS é um problema de saúde pública no mundo. Em 2014, foram notificados 9.888 novos casos no Brasil e estima-se que metade dos pacientes desconhecem ser portadores da doença. O sarcoma de Kaposi associado à AIDS (KS-AIDS) é um marcador de progressão da doença e imunossupressão. Embora a incidência de SK-AIDS na cavidade oral tenha diminuído notavelmente desde o acesso universal ao tratamento retroviral altamente ativo, há estudos em São paulo que estabelecem uma incidência dessa neoplasia em 5%. A síndrome de reconstituição imunológica associada ao KS-AIDS e ao linfedema facial é uma complicação com risco de vida. A falta de treinamento no diagnóstico oral do SK-AIDS e sua incidência relativamente baixa podem fazer com que essa neoplasia passe despercebida pelo clínico no exame de rotina, sendo este um sinal clínico característico de imunossupressão. Este artigo analisa o SK oral associado à AIDS.

Incidental Adrenocortical Carcinoma in Dogs: Clinical, Tomographic and Histopathological

Background: Adrenal incidentalomas are masses accidentally discovered during imaging examinations performed when there is no suspicion of adrenal disease. Even with a low prevalence, it is important to perform a reliable evaluation observing biological behavior and determining whether the hormonal activity is stimulated. Frequently, these masses are not functional, but in some cases, there is increased cortisol activity, and patients with adrenal incidentalomas may present hyperadrenocorticism. This report aims to describe the clinical, tomographic, and histopathological aspects of a case of adrenal incidentaloma detected in a routine abdominal ultrasound.Case: An 8-year-old, male, maltese dog with occasional emesis, halitosis, claudication of the left pelvic limb, and previous compensated and untreated cardiomyopathy was treated at the Veterinary Hospital of the Federal University of Mato Grosso (HOVET-UFMT). Physical examination revealed arterial hypertension and claudication, with the positive posterior drawer test suggesting rupture of the cruciate ligament. The blood count showed no alteration, and the serum biochemistry revealed a slight increase in the activity of alanine aminotransferase. In order to investigate this increase, an abdominal ultrasound was performed. Slight hepatomegaly and a heterogeneous mass of irregular edges were observed with a moderate and difficult-to-delimit vascularization of the adrenal gland. Left knee radiography raised the suspicion of rupture of the cranial cruciate ligament due to the cranial displacement of the tibia in relation to the femur. Computed tomography was performed to define the extent and delimitation of the mass, which was compatible with a tumor of the right adrenal gland characterized by the visualization of an abdominal mass between the kidneys, extending from the hepatic region to the cranial pole of the left kidney. On follow-up, the patient was reported to have diarrhea with black stools, and a low-dose dexamethasone suppression test was ordered. Unilateral adrenalectomy was recommended due to the suspicion of pheochromocytoma. During the surgical procedure, the mass adhered to the abdominal wall and the diaphragm resulting in the death of the animal. Histopathological analysis revealed a cellular proliferation of cortical adrenal cells forming multiple cell nests separated by a small amount of fibrovascular stroma. Proliferated cells were polyhedral, with densely eosinophilic cytoplasm and well-defined edges, and were occasionally vesicular. They had globular nuclei, slightly stained chromatin, and inconspicuous nucleoli. Pleomorphism, anisocytosis, and anisokaryosis were accentuated, and eight mitosis figures were observed in ten high-power fields (40×), leading to a diagnosis of adrenocortical carcinoma.Discussion: When there is no suspicion or characteristic clinical sign, and adrenal growth is observed on imaging examination, the finding may be called an incidentaloma. Here, the incidentaloma was a non-functional adrenal carcinoma, because the tests were not conclusive. Adrenal carcinomas grow by infiltrating adjacent tissues, such as the caudal vena cava. In this case, it infiltrated the abdominal wall and diaphragm. Therefore, imaging, ultrasound, and tomography examinations were important for the characterization of the adrenal incidentaloma in this dog. This adrenal incidentaloma, which was a carcinoma with metastasis to the adjacent tissues, required other hormonal tests to rule out further endocrine dysfunctions.

Allogeneic fibroblast cell therapy in the treatment of recessive dystrophic epidermolysis bullosa

Abstract Background The non-healing wound is a characteristic clinical sign in recessive dystrophic epidermolysis bullosa (RDEB). Methods Six patients with recessive dystrophic epidermolysis bullosa were injected with suspension of allogeneic fibroblasts into erosion margins. Erosions (>1 month old) with surface area between 2 cm2 and 28 cm2 were selected for treatment. The patients were administered with 1 mL suspension of allogeneic fibroblasts with concentration 5 × 106 cells/ml, 10 × 106 cells/ml and 20 × 106 cells/ml. Paired erosions were injected with vehicle solution alone. All erosions were assessed for healing rate and biopsied at baseline and at two weeks after treatment. Immunofluorescence antigen mapping (IFM) was performed to detect C7 expression. Results An increase of healing rate was detected 14 days after fibroblasts and vehicle alone injections, in some cases with complete erosion closure. The results of the IFM in patients treated with allogeneic fibroblasts and vehicle solution demonstrated the increase of collagen VII expression in dermo-epidermal junction, more intensive in patients injected with 20 × 106 cells/ml. Conclusions Intradermal administration of allogeneic fibroblasts is a safe and effective method of treatment of non-healing wounds in recessive dystrophic epidermolysis bullosa.

Therapeutic approach of laryngeal polyps

Laryngeal polyps are the most frequent benign tumors of the vocal folds. The most characteristic clinical sign is dominated by the sudden onset of dysphonia which becomes permanent in time. Vocal abuse is incriminated in literature as the predominant etiological factor. Often, the vocal fold polyp is unilateral, situated in the membranous part of the vocal fold, and can reach an ample size, leading to consecutive glottis obstruction. The authors present the main therapeutic approach applied on a patient admitted in the clinic with this benign pathology. The therapeutic management consisted in complete tumor resection using endoscopic “cold steel” techniques combined with laser CO2, followed by postoperative speech therapy.

ПЕРВЫЙ ОПЫТ ВИДЕОТОРАКОСКОПИЧЕСКОЙ ВЕРХНЕГРУДНОЙ СИМПАТЭКТОМИИ при феномене Ре

Objective: To study the results of the first experience of endoscopic upper-pectoral sympathectomy (UPS) under the Raynaud’s phenomenon. Methods: The results of the performance of video thoracoscopic UPS in 16 patients with the idiopathic form of the Raynaud’s phenomenon are analyzed. Women were 12 (75%), men – 4 (25%) at the age of 14 to 24 years (the average age was 24.9±3.7 years). All patients had a second stage of the disease with symptoms of chronic ischemia of hands II-III degrees. The average duration of the onset of the disease till the operative treatment was 3.2±0.4 years. Results: A characteristic clinical sign of the disease was the symmetrical affection of the hands with the phenomena of cyanosis, hyperemia, mottled skin and hyperhidrosis. According to Doppler Scan, in all cases, a decrease in the linear velocity of the blood flow in the arteries of the forearm, hand and fingers, increasing of index resistibility with reduction of the pulsating index. All 16 patients underwent videothoracoscopic UPS. The duration of the operation was 98.5±10.5 min. Intra- and postoperative complications were not observed. In the nearest postoperative period no complications were observed, the regress of Raynaud’s symptoms was noted, an increase in the blood flow velocity was recorded in the arteries of the hands and fingers in the Ultrasound Diagnostic. A year later, in the cold season, a part of patients (n=3) again have moderate signs of the disease; these patients underwent complex conservative therapy. Remote results are in the studying stage. Conclusion: The UPS, by any means, is performed, is an effective and reasonable procedure. Timely surgical treatment prevents the progression of the disease and the development of complications and improves the quality of life of patients. Keywords: Raynaud phenomenon, hand’s ischemia, sympathectomy, video-thoracoscopy.

ERYTHEMA NODOSUM AS A TYPE OF SEPTAL PANNICULITIS IN RHEUMATOLOGIC PRACTICE: EVALUATION OF THE COURSE AND OUTCOMES

Study objective: to study clinical and laboratory peculiarities of EN depending on the etiological agent as well as to determine disease recurrence risk factors. Materials and methods: the study included 121 patient with EN. Depending on the reason of origin all patients were divided into three groups: EN with sL (66 subjects), EN in pregnant women (23 subjects) and infectionassociated EN (32 persons). The work evaluated peculiarities of the course and outcomes of EN for each of the groups. Results: Clinical and laboratory characteristics was on the whole comparable in groups with infection associated EN and EN in pregnancy, but was sharply different from those observed in sL. In the recent case a considerable increase of inflammatory activity values was noted as well. A characteristic clinical sign of infection-associated EN is a symptom of the “bruise blossoming”. The recurrence in groups of EN in pregnancy and in sL was observed in ¼ of cases. In the infection-associated EN group the recurrence took place in 40% of case, which was due to lower therapeutic effect from antivirals and greater disposition of the viral infection to chronicity.

IL-31-induced pruritus in dogs: a novel experimental model to evaluate anti-pruritic effects of canine therapeutics.

BackgroundPruritus is a characteristic clinical sign of allergic skin conditions including atopic dermatitis (AD) in the dog. IL‐31 is a cytokine found in the serum of some dogs with AD and can induce pruritic behaviours in laboratory beagle dogs.Hypothesis/ObjectivesThe objectives were to characterize an IL‐31‐induced pruritus model by evaluating the efficacy of prednisolone, dexamethasone and oclacitinib, and to compare the speed of anti‐pruritic effects of oclacitinib against those of prednisolone and dexamethasone.AnimalsPurpose‐bred beagle dogs were used in all studies.MethodsRandomized, blinded, placebo‐controlled studies were designed to evaluate and compare the anti‐pruritic properties of prednisolone, dexamethasone and oclacitinib following a single intravenous injection of recombinant canine IL‐31. Video surveillance was used to monitor and score pruritic behaviours in study animals.ResultsPrednisolone [0.5 mg/kg, per os (p.o.)] reduced IL‐31‐induced pruritus when given 10 h prior to observation. When the time interval between drug treatment and observation was shortened to 1 h, dexamethasone (0.2 mg/kg, intramuscular) but not prednisolone (0.25 or 0.5 mg/kg, p.o.) reduced IL‐31‐induced pruritus. Oclacitinib (0.4 mg/kg, p.o.) reduced pruritus when given 1, 6, 11 and 16 h prior to the observation period, and the anti‐pruritic activity of oclacitinib was greater when compared to prednisolone and dexamethasone at all time points assessed.Conclusion and clinical importanceThe efficacy of prednisolone, dexamethasone and oclacitinib in the IL‐31‐induced pruritus model gives confidence that this may be a relevant model for acute pruritus associated with allergic dermatitis including AD and can be used to evaluate novel compounds or formulations.

Another potential carp killer?: Carp Edema Virus disease in Germany.

BackgroundInfections with carp edema virus, a pox virus, are known from Japanese koi populations since 1974. A characteristic clinical sign associated with this infection is lethargy and therefore the disease is called “koi sleepy disease”. Diseased koi also show swollen gills, enophthalmus, and skin lesions. Mortality rates up to 80 % are described. For a long period of time, disease outbreaks seemed to be restricted to Japan. However, during the last years clinical outbreaks of koi sleepy disease also occurred in the UK and in the Netherlands.Case presentationIn spring 2014 koi from different ponds showing lethargic behavior, skin ulcers, inflammation of the anus, enophthalmus, and gill necrosis were presented to the laboratory for diagnosis. In all cases, new koi had been purchased earlier that spring from the same retailer and introduced into existing populations. Eleven koi from six ponds were examined for ectoparasites and for bacterial and viral infections (cyprinid herpesviruses in general and especially koi herpesvirus (KHV) known formally as Cyprinid herpesvirus 3 (CyHV–3); and Carp Edema Virus). In most of the cases parasites were not detected from skin and gills. Only opportunistic freshwater bacteria were isolated from skin ulcers. In cell cultures no cytopathic effect was observed, and none of the samples gave positive results in PCR tests for cyprinid herpesviruses. By analyzing gill tissues for CEV in seven out of eleven samples by a nested PCR, PCR products of 547 bp and 180 bp (by using nested primers) could be amplified. An outbreak of Koi Sleepy Disease was confirmed by sequencing of the PCR products. These results confirm the presence of CEV in German koi populations.ConclusionA clinical outbreak of “koi sleepy disease” due to an infection with Carp Edema Virus was confirmed for the first time in Germany. To avoid transmission of CEV to common carp testing of CEV should become part of fish disease surveillance programs.Electronic supplementary materialThe online version of this article (doi:10.1186/s12917-015-0424-7) contains supplementary material, which is available to authorized users.

Epispadias and urethral duplication

Epispadias is the mildest form of the exstrophy-epispadias complex and rarely occurs in an isolated form. The characteristic clinical sign is a mucosal strip on the penile dorsum. Clinically, epispadias presents with urinary incontinence. Primary surgical correction is recommended at the age of 12 months and should only be performed at a specialized center. During follow-up, further bladder neck surgery may be necessary. Despite a functional and cosmetically appealing penis, psychosocial and psychosexual development of the affected individuals can severely be affected. The incidence of urethral duplication remains unclear. Several classifications reflect the anatomical variation. The clinical presentation depends on the continuity of the duplicated urethra and its relationship to the sphincteric mechanism. In addition to clinical examination, a voiding cysturethrography is part of the basic diagnostic workup. After endoscopic examination an individual operative approach can be defined.

Neurophysiological evidence for generalized sensory neuronopathy in cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome.

Cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (CANVAS) is a recently described multisystem ataxia defined by the presence of cerebellar ataxia, bilateral vestibulopathy, and a somatosensory deficit. The characteristic clinical sign is an abnormal visually enhanced vestibuloocular reflex. The somatosensory deficit contributes to a significant level of disability in CANVAS. This study was a neurophysiological investigation of 14 patients with CANVAS. Findings revealed uniformly absent sensory nerve action potentials in all limbs, abnormal blink reflexes in 13 of 14 patients, and abnormal masseter reflexes in 6 of 11 patients. Tibial H-reflexes were absent in 11 of 14 patients. Somatosensory evoked potentials were abnormal in 10 of the 11 patients tested, and brainstem auditory evoked responses were abnormal in 3 of 8. Cutaneous silent period responses were abnormal in 7 of 14 patients. We suggest that a sensory neuronopathy should be sought in cerebellar and/or vestibular ataxias, particularly where the degree of ataxia is out of proportion to the clinically identified cerebellar and/or vestibular dysfunction.

CANVAS an update: clinical presentation, investigation and management.

Cerebellar Ataxia with Neuropathy and bilateral Vestibular Areflexia Syndrome (CANVAS) is a multi-system ataxia which results in cerebellar ataxia, a bilateral vestibulopathy and a somatosensory deficit. This sensory deficit has recently been shown to be a neuronopathy, with marked dorsal root ganglia neuronal loss. The characteristic oculomotor clinical sign is an abnormal visually enhanced vestibulo-ocular reflex. To outline the expanding understanding of the pathology in this condition, as well as diagnostic and management issues encountered in clinical practice. Retrospective data on 80 CANVAS patients is reviewed. In addition to the triad of cerebellar impairment, bilateral vestibulopathy and a somatosensory deficit, CANVAS patients may also present with orthostatic hypotension, a chronic cough and neuropathic pain. Management of falls risk and dysphagia is a major clinical priority. CANVAS is an increasingly recognised cause of late-onset ataxia and disequilibrium, and is likely to be a recessive disorder.

The pivotal sign of CANVAS

A 75-year-old woman complained about insecure gait since age 55. Clinical examination revealed signs of cerebellar ataxia, bilateral vestibulopathy, and peripheral sensory impairment. Sensory nerve action potentials were absent. The visually enhanced vestibulo-ocular reflex (VVOR) was impaired (video on the Neurology(®) Web site at www.neurology.org, figure 1) and the diagnosis of cerebellar ataxia (figure 2) with neuropathy and bilateral vestibular areflexia syndrome (CANVAS) was made.(1) CANVAS is considered to be a recessive disorder with a mean age at onset of 60 years.(2) VVOR impairment is its characteristic clinical sign.(2) It can only be elicited if both smooth-pursuit eye movements and the vestibulo-ocular reflex are deficient. Normally, both are redundant at low head velocities.(2.)

First WNK4-Hypokalemia Animal Model Identified by Genome-Wide Association in Burmese Cats

Burmese is an old and popular cat breed, however, several health concerns, such as hypokalemia and a craniofacial defect, are prevalent, endangering the general health of the breed. Hypokalemia, a subnormal serum potassium ion concentration ([K+]), most often occurs as a secondary problem but can occur as a primary problem, such as hypokalaemic periodic paralysis in humans, and as feline hypokalaemic periodic polymyopathy primarily in Burmese. The most characteristic clinical sign of hypokalemia in Burmese is a skeletal muscle weakness that is frequently episodic in nature, either generalized, or sometimes localized to the cervical and thoracic limb girdle muscles. Burmese hypokalemia is suspected to be a single locus autosomal recessive trait. A genome wide case-control study using the illumina Infinium Feline 63K iSelect DNA array was performed using 35 cases and 25 controls from the Burmese breed that identified a locus on chromosome E1 associated with hypokalemia. Within approximately 1.2 Mb of the highest associated SNP, two candidate genes were identified, KCNH4 and WNK4. Direct sequencing of the genes revealed a nonsense mutation, producing a premature stop codon within WNK4 (c.2899C>T), leading to a truncated protein that lacks the C-terminal coiled-coil domain and the highly conserved Akt1/SGK phosphorylation site. All cases were homozygous for the mutation. Although the exact mechanism causing hypokalemia has not been determined, extrapolation from the homologous human and mouse genes suggests the mechanism may involve a potassium-losing nephropathy. A genetic test to screen for the genetic defect within the active breeding population has been developed, which should lead to eradication of the mutation and improved general health within the breed. Moreover, the identified mutation may help clarify the role of the protein in K+ regulation and the cat represents the first animal model for WNK4-associated hypokalemia.

Levodopa increases speed of alternating movements in Parkinson’s disease patients

Disturbances of alternating movement execution are a characteristic clinical sign of patients with Parkinson's disease (PD). Objectives were to compare instrumentally measured diadochokinetic motion series carrying out before and 1h after standardised levodopa intake and to correlate the device results with the respective rating scores of the PD patients. Maximum velocity and interval improved following levodopa application. The amplitude of motions did not differ between both assessment moments. Closer correlations between rating- and diadochokinesimeter outcomes appeared before levodopa intake.

Cerebellar Ataxia With Neuropathy and Bilateral Vestibular Areflexia Syndrome

Szmulewicz, David J.*; Merchant, Saumil N.†; Halmagyi, Gabor Michael‡ Author Information

Cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS): a review of the clinical features and video‐oculographic diagnosis

The association of bilateral vestibulopathy with cerebellar ataxia was first reported in 1991 and delineated as a distinct syndrome with a characteristic and measurable clinical sign--an absent visually enhanced vestibulo-ocular reflex--in 2004. We reviewed 27 patients with this syndrome and show that a non-length-dependent sensory deficit with absent sensory nerve action potentials is an integral component of this syndrome, which we now call "cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome" (CANVAS). All patients had brain MRI and 22/27 had evidence of cerebellar atrophy involving anterior and dorsal vermis, as well as the hemispheric crus I. Brain and temporal bone pathology in one patient showed marked loss of Purkinje cells and of vestibular, trigeminal, and facial ganglion cells, but not of spiral ganglion cells. There are two sets of sibling pairs, suggesting CANVAS is a late-onset recessive disorder. The characteristic clinical sign-the visual vestibulo-ocular reflex deficit-can be demonstrated and measured clinically using video-oculography.