Early non-disabling relapses are important predictors of disability accumulation in people with relapsing-remitting multiple sclerosis.

BACKGROUND: The prognostic significance of non-disabling relapses in people with relapsing-remitting multiple sclerosis (RRMS) is unclear. OBJECTIVE: To determine whether early non-disabling relapses predict disability accumulation in RRMS. METHODS: We redefined mild relapses in MSBase as 'non-disabling', and moderate or severe relapses as 'disabling'. We used mixed-effects Cox models to compare 90-day confirmed disability accumulation events in people with exclusively non-disabling relapses within 2 years of RRMS diagnosis to those with no early relapses; and any early disabling relapses. Analyses were stratified by disease-modifying therapy (DMT) efficacy during follow-up. RESULTS: People who experienced non-disabling relapses within 2 years of RRMS diagnosis accumulated more disability than those with no early relapses if they were untreated (n = 285 vs 4717; hazard ratio (HR) = 1.29, 95% confidence interval (CI) = 1.00-1.68) or given platform DMTs (n = 1074 vs 7262; HR = 1.33, 95% CI = 1.15-1.54), but not if given high-efficacy DMTs (n = 572 vs 3534; HR = 0.90, 95% CI = 0.71-1.13) during follow-up. Differences in disability accumulation between those with early non-disabling relapses and those with early disabling relapses were not confirmed statistically. CONCLUSION: This study suggests that early non-disabling relapses are associated with a higher risk of disability accumulation than no early relapses in RRMS. This risk may be mitigated by high-efficacy DMTs. Therefore, non-disabling relapses should be considered when making treatment decisions.

Redefining the Multiple Sclerosis Severity Score (MSSS): The effect of sex and onset phenotype.

BACKGROUND: The Multiple Sclerosis Severity Score (MSSS) is a widely used measure of the disability progression rate. However, the global MSSS may not be the best basis for comparison between all patient groups. OBJECTIVE: We evaluated sex-specific and onset phenotype-specific MSSS matrices to determine if they were more effective than the global MSSS as a basis for comparison within these subsets. METHODS: Using a large international dataset of multiple sclerosis (MS) patient records and the original MSSS algorithm, we constructed global, sex-specific and onset phenotype-specific MSSS matrices. We compared matrices using permutation analysis. RESULTS: Our final dataset included 30,203 MS cases, with 28.9% males and 6.5% progressive-onset cases. Our global MSSS matrix did not differ from previously published data (p > 0.05). The progressive-onset-specific matrix differed significantly from the relapsing-onset-specific matrix (p < 0.001), with lower MSSS attributed to cases with the same Expanded Disability Status Score (EDSS) and disease duration. When evaluated with a simulation, using an onset-specific MSSS improved statistical power in mixed cohorts. There were no significant differences by sex. CONCLUSION: The differences in the disability accrual rate between progressive- and relapsing-onset MS have a significant effect on MSSS. An onset-specific MSSS should be used when comparing the rate of disability progression among progressive-onset cases and for mixed cohorts.

Prognostic indicators in pediatric clinically isolated syndrome.

OBJECTIVE: To assess prognostic factors for a second clinical attack and a first disability-worsening event in pediatric clinically isolated syndrome (pCIS) suggestive of multiple sclerosis (MS) patients. METHODS: A cohort of 770 pCIS patients was followed up for at least 10 years. Cox proportional hazard models and Recursive Partitioning and Amalgamation (RECPAM) tree-regression were used to analyze data. RESULTS: In pCIS, female sex and a multifocal onset were risk factors for a second clinical attack (hazard ratio [HR], 95% confidence interval [CI] = 1.28, 1.06-1.55; 1.42, 1.10-1.84, respectively), whereas disease-modifying drug (DMD) exposure reduced this risk (HR, 95% CI = 0.75, 0.60-0.95). After pediatric onset MS (POMS) diagnosis, age at onset younger than 15 years and DMD exposure decreased the risk of a first Expanded Disability Status Scale (EDSS)-worsening event (HR, 95% CI = 0.59, 0.42-0.83; 0.75, 0.71-0.80, respectively), whereas the occurrence of relapse increased this risk (HR, 95% CI = 5.08, 3.46-7.46). An exploratory RECPAM analysis highlighted a significantly higher incidence of a first EDSS-worsening event in patients with multifocal or isolated spinal cord or optic neuritis involvement at onset in comparison to those with an isolated supratentorial or brainstem syndrome. A Cox regression model including RECPAM classes confirmed DMD exposure as the most protective factor against EDSS-worsening events and relapses as the most important risk factor for attaining EDSS worsening. INTERPRETATION: This work represents a step forward in identifying predictors of unfavorable course in pCIS and POMS and supports a protective effect of early DMD treatment in preventing MS development and disability accumulation in this population. Ann Neurol 2017;81:729-739.

Long-term disability trajectories in primary progressive MS patients: A latent class growth analysis.

BACKGROUND: Several natural history studies on primary progressive multiple sclerosis (PPMS) patients detected a consistent heterogeneity in the rate of disability accumulation. OBJECTIVES: To identify subgroups of PPMS patients with similar longitudinal trajectories of Expanded Disability Status Scale (EDSS) over time. METHODS: All PPMS patients collected within the MSBase registry, who had their first EDSS assessment within 5 years from onset, were included in the analysis. Longitudinal EDSS scores were modeled by a latent class mixed model (LCMM), using a nonlinear function of time from onset. LCMM is an advanced statistical approach that models heterogeneity between patients by classifying them into unobserved groups showing similar characteristics. RESULTS: A total of 853 PPMS (51.7% females) from 24 countries with a mean age at onset of 42.4 years (standard deviation (SD): 10.8 years), a median baseline EDSS of 4 (interquartile range (IQR): 2.5-5.5), and 2.4 years of disease duration (SD: 1.5 years) were included. LCMM detected three different subgroups of patients with a mild ( n = 143; 16.8%), moderate ( n = 378; 44.3%), or severe ( n = 332; 38.9%) disability trajectory. The probability of reaching EDSS 6 at 10 years was 0%, 46.4%, and 81.9% respectively. CONCLUSION: Applying an LCMM modeling approach to long-term EDSS data, it is possible to identify groups of PPMS patients with different prognosis.

Higher latitude is significantly associated with an earlier age of disease onset in multiple sclerosis.

BACKGROUND: Age at onset (AAO) in multiple sclerosis (MS) is an important marker of disease severity and may have prognostic significance. Understanding what factors can influence AAO may shed light on the aetiology of this complex disease, and have applications in the diagnostic process. METHODS: The study cohort of 22 162 eligible patients from 21 countries was extracted from the MSBase registry. Only patients with MS aged ≥16 years were included. To reduce heterogeneity, only centres of largely European descent were included for analysis. AAO was defined as the year of the first symptom suggestive of inflammatory central nervous system demyelination. Predictors of AAO were evaluated by linear regression. RESULTS: Compared with those living in lower latitudes (19.0-39.9°), onset of symptoms was 1.9 years earlier for those at higher latitudes (50.0-56.0°) (p=3.83×10-23). A reciprocal relationship was seen for ambient ultraviolet radiation (UVR), with a significantly increasing AAO for patients with MS per each quartile increment of ambient UVR (p=1.56×10-17). We found that the AAO of female patients was ∼5 months earlier than male patients (p=0.002). AAO of progressive-onset patients with MS were ∼9 years later than relapsing-onset patients (p=1.40×10-265). CONCLUSIONS: An earlier AAO in higher latitude regions was found in this worldwide European-descent cohort and correlated inversely with variation in latitudinal UVR. These results suggest that environmental factors which act at the population level may significantly influence disease severity characteristics in genetically susceptible populations.

Incidence of first ever stroke during Hajj ceremony.

BACKGROUND: The Hajj Ceremony, the largest annual gathering in the world, is the most important life event for any Muslim. This study was designed to evaluate the incidence of stroke among Iranian pilgrims during the Hajj ceremony. METHODS: We ascertained all cases of stroke occurring in a population of 92,974 Iranian pilgrims between November 27, 2007 and January 12, 2008. Incidence and risk factors of the first ever stroke in Hajj pilgrims were compared, within the same time frame, to those of the Mashhad residents, the second largest city in Iran. Data for the latter group were extracted from the Mashhad Stroke Incidence Study (MSIS) database. RESULTS: During the study period, 17 first-ever strokes occurred in the Hajj pilgrims and 40 first-ever stroke strokes occurred in the MSIS group. Overall, the adjusted incidence rate of first ever stroke in the Hajj cohort was lower than that of the MSIS population (9 vs. 16 per 100,000). For age- and gender-specific subgroups, the Hajj stroke crude rates were in general similar to or lower than the general population of Mashhad, Iran, with the exception of women aged 35 to 44 years and aged >75 years who were at greater risk of having first-ever stroke than the non-pilgrims of the same age. CONCLUSION: The first ever stroke rate among Iranian Hajj pilgrims was lower than that of the general population in Mashhad, Iran, except for females 35-44 or more than 75 years old. The number of events occurring during the Hajj suggests that Islamic countries should consider designing preventive and screening programs for pilgrims.

Predictors of treatment switching in the Big Multiple Sclerosis Data Network.

Background: Treatment switching is a common challenge and opportunity in real-world clinical practice. Increasing diversity in disease-modifying treatments (DMTs) has generated interest in the identification of reliable and robust predictors of treatment switching across different countries, DMTs, and time periods. Objective: The objective of this retrospective, observational study was to identify independent predictors of treatment switching in a population of relapsing-remitting MS (RRMS) patients in the Big Multiple Sclerosis Data Network of national clinical registries, including the Italian MS registry, the OFSEP of France, the Danish MS registry, the Swedish national MS registry, and the international MSBase Registry. Methods: In this cohort study, we merged information on 269,822 treatment episodes in 110,326 patients from 1997 to 2018 from five clinical registries. Patients were included in the final pooled analysis set if they had initiated at least one DMT during the relapsing-remitting MS (RRMS) stage. Patients not diagnosed with RRMS or RRMS patients not initiating DMT therapy during the RRMS phase were excluded from the analysis. The primary study outcome was treatment switching. A multilevel mixed-effects shared frailty time-to-event model was used to identify independent predictors of treatment switching. The contributing MS registry was included in the pooled analysis as a random effect. Results: Every one-point increase in the Expanded Disability Status Scale (EDSS) score at treatment start was associated with 1.08 times the rate of subsequent switching, adjusting for age, sex, and calendar year (adjusted hazard ratio [aHR] 1.08; 95% CI 1.07-1.08). Women were associated with 1.11 times the rate of switching relative to men (95% CI 1.08-1.14), whilst older age was also associated with an increased rate of treatment switching. DMTs started between 2007 and 2012 were associated with 2.48 times the rate of switching relative to DMTs that began between 1996 and 2006 (aHR 2.48; 95% CI 2.48-2.56). DMTs started from 2013 onwards were more likely to switch relative to the earlier treatment epoch (aHR 8.09; 95% CI 7.79-8.41; reference = 1996-2006). Conclusion: Switching between DMTs is associated with female sex, age, and disability at baseline and has increased in frequency considerably in recent years as more treatment options have become available. Consideration of a patient's individual risk and tolerance profile needs to be taken into account when selecting the most appropriate switch therapy from an expanding array of treatment choices.

Geomagnetic disturbances may be environmental risk factor for multiple sclerosis: an ecological study of 111 locations in 24 countries.

BACKGROUND: We noticed that a hypothesis based on the effect of geomagnetic disturbances (GMD) has the ability to explain special features of multiple sclerosis (MS). Areas around geomagnetic 60 degree latitude (GM60L) experience the greatest amount of GMD. The easiest way to evaluate our hypothesis was to test the association of MS prevalence (MSP) with angular distance to geomagnetic 60 degree latitude (AMAG60) and compare it with the known association of MS with geographical latitude (GL). We did the same with angular distance to geographic 60 degree latitude (AGRAPH60) as a control. METHODS: English written papers with MSP keywords, done in Europe (EUR), North America (NA) or Australasia (AUS) were retrieved from the PubMed. Geomagnetic coordinates were determined for each location and AMAG60 was calculated as absolute value of numerical difference between its geomagnetic latitude from GM60L. By an ecological study with using meta-regression analyses, the relationship of MSP with GL, AMAG60 and AGRAPH60 were evaluated separately. MSP data were weighted by square root of number of prevalent cases. Models were compared by their adjusted R square (AR2) and standard error of estimate (SEE). RESULTS: 111 MSP data were entered in the study. In each continent, AMAG60 had the best correlation with MSP, the largest AR2 (0.47, 0.42 and 0.84 for EUR, NA and AUS, respectively) and the least SEE. Merging both hemispheres data, AMAG60 explained 56% of MSP variations with the least SEE (R = 0.75, AR2 = 0.56, SEE = 57), while GL explained 17% (R = 0.41, AR2 = 0.17, SEE = 78.5) and AGRAPH60 explained 12% of that variations with the highest SEE (R = 0.35, AR2 = 0.12, SEE = 80.5). CONCLUSIONS: Our results confirmed that AMAG60 is the best describer of MSP variations and has the strongest association with MSP distribution. They clarified that the well-known latitudinal gradient of MSP may be actually a gradient related to GM60L. Moreover, the location of GM60L can elucidate why MSP has parabolic and linear gradient in the north and south hemisphere, respectively. This preliminary evaluation supported that GMD can be the mysterious environmental risk factor for MS. We believe that this hypothesis deserves to be considered for further validation studies.

Risk of stroke in hospitalized SARS-CoV-2 infected patients: A multinational study.

BACKGROUND: There is an increased attention to stroke following SARS-CoV-2. The goal of this study was to better depict the short-term risk of stroke and its associated factors among SARS-CoV-2 hospitalized patients. METHODS: This multicentre, multinational observational study includes hospitalized SARS-CoV-2 patients from North and South America (United States, Canada, and Brazil), Europe (Greece, Italy, Finland, and Turkey), Asia (Lebanon, Iran, and India), and Oceania (New Zealand). The outcome was the risk of subsequent stroke. Centres were included by non-probability sampling. The counts and clinical characteristics including laboratory findings and imaging of the patients with and without a subsequent stroke were recorded according to a predefined protocol. Quality, risk of bias, and heterogeneity assessments were conducted according to ROBINS-E and Cochrane Q-test. The risk of subsequent stroke was estimated through meta-analyses with random effect models. Bivariate logistic regression was used to determine the parameters with predictive outcome value. The study was reported according to the STROBE, MOOSE, and EQUATOR guidelines. FINDINGS: We received data from 26,175 hospitalized SARS-CoV-2 patients from 99 tertiary centres in 65 regions of 11 countries until May 1st, 2020. A total of 17,799 patients were included in meta-analyses. Among them, 156(0.9%) patients had a stroke-123(79%) ischaemic stroke, 27(17%) intracerebral/subarachnoid hemorrhage, and 6(4%) cerebral sinus thrombosis. Subsequent stroke risks calculated with meta-analyses, under low to moderate heterogeneity, were 0.5% among all centres in all countries, and 0.7% among countries with higher health expenditures. The need for mechanical ventilation (OR: 1.9, 95% CI:1.1-3.5, p = 0.03) and the presence of ischaemic heart disease (OR: 2.5, 95% CI:1.4-4.7, p = 0.006) were predictive of stroke. INTERPRETATION: The results of this multi-national study on hospitalized patients with SARS-CoV-2 infection indicated an overall stroke risk of 0.5%(pooled risk: 0.9%). The need for mechanical ventilation and the history of ischaemic heart disease are the independent predictors of stroke among SARS-CoV-2 patients. FUNDING: None.

Which Environmental Factor Is Correlated with Long-Term Multiple Sclerosis Incidence Trends: Ultraviolet B Radiation or Geomagnetic Disturbances?

BACKGROUND: Insufficient received ultraviolet B radiation (UV) is regarded as the main environmental risk factor (RF) for MS in vitamin D deficiency hypothesis. Nevertheless, geomagnetic disturbance (GMD) has also been proposed as a potential trigger for MS in GMD hypothesis. The aim of this study was to investigate which of these mentioned RF is correlated with long-term ultradecadal MS incidence. METHODS: After a systematic search, long-term incidence reports of the United Kingdom (UK), Denmark, Tayside County, Nordland County, the Orkney, and Shetland Islands were selected for this retrospective time-series study. Possible lead-lag relationships between MS incidence, GMD, and UV were evaluated by cross-correlation analysis. RESULTS: Significant positive correlations between GMD and MS incidence were seen in Tayside County (at lag of 2 years: rS = 0.38), Denmark (peak correlation at lag of 2 years: rS = 0.53), and UK (at lag of 1 year: rS = 0.50). We found a positive correlation between received UV and MS incidences in the Nordland at lag of 1 year (rS = 0.49). CONCLUSION: This study found significant positive correlations between alterations in GMD with alterations in long-term MS incidence in three out of six studied locations and supports the GMD hypothesis. The observed significant correlation between MS and UV is positive; hence it is not supportive for UV related vitamin D deficiency hypothesis.

Correlation of multiple sclerosis (MS) incidence trends with solar and geomagnetic indices: Time to revise the method of reporting MS epidemiological data.

BACKGROUND: Recently, we introduced solar related geomagnetic disturbances (GMD) as a potential environmental risk factor for multiple sclerosis (MS). The aim of this study was to test probable correlation between solar activities and GMD with long-term variations of MS incidence. METHODS: After a systematic review, we studied the association betwee n alterations in the solar wind velocity (VSW) and planetary A index (AP, a GMD index) with MS incidence in Tehran and western Greece, during the 23(rd) solar cycle (1996-2008), by an ecological-correlational study. RESULTS: We found moderate to strong correlations among MS incidence of Tehran with VSW (rS = 0.665, P = 0.013), with 1 year delay, and also with AP (rS = 0.864, P = 0.001) with 2 year delay. There were very strong correlations among MS incidence data of Greece with VSW (r = 0.906, P < 0.001) and with AP (r = 0.844, P = 0.001), both with 1 year lag. CONCLUSION: It is the first time that a hypothesis has introduced an environmental factor that may describe MS incidence alterations; however, it should be reminded that correlation does not mean necessarily the existence of a causal relationship. Important message of these findings for researchers is to provide MS incidence reports with higher resolution for consecutive years, based on the time of disease onset and relapses, not just the time of diagnosis. Then, it would be possible to further investigate the validity of GMD hypothesis or any other probable environmental risk factors.

The effect of lithium in post-stroke motor recovery: a double-blind, placebo-controlled, randomized clinical trial.

OBJECTIVE: Evidences from cultured cells and animal models of ischemia suggest that lithium has neuroprotective and neurotrophic effects and may play a desirable role in reducing infarct volume and even improving the brain insults from stroke. The aim of this study was to evaluate the efficacy of lithium in early motor recovery of patients after ischemic stroke. METHODS: Eighty patients with first ever stroke, allocated randomly in lithium, 300 mg twice daily, or placebo. Treatment was initiated 48 hours after stroke and continued for 30 days. Modified National Institute of Health Stroke Scale (mNIHSS) and hand subsection of Fugl-Meyer Assessment (hFMA) were used to evaluate impairment on the fifth and 30th day of treatment. RESULTS: Sixty-six subjects (32 subjects in the lithium group and 34 subjects in the placebo group) completed the study. There were no significant differences in the improvement in mNIHSS (P=0.40) and hFMA (P=0.07) after 30 days. However, a subgroup analysis showed that patients with cortical strokes in the lithium group had significantly better improvement in both mNIHSS and hFMA in comparison to the placebo group (P=0.003). Approximately 44% (n=14) of patients in the lithium group, mainly from the cortical stroke subgroup, regained more than 25% of full function based on hFMA, whereas this rate in the placebo group was 14.7% (n=5; P=0.009). CONCLUSION: The observed discrete difference between the lithium group and the placebo group in the cortical stroke subgroup may suggest an enhanced motor recovery after stroke by using an early treatment with a low dose of lithium carbonate. However, a larger trial with more patients with cortical stroke is needed to investigate this effect better.

Can STOP Trial Velocity Criteria Be Applied to Iranian Children with Sickle Cell Disease?

BACKGROUND AND PURPOSE: Sickle cell disease (SCD) is strongly linked to stroke across all haplotypes in the pediatric population. Transcranial Doppler (TCD) ultrasound is known to identify the highest risk group in African-Americans who need to receive and stay on blood transfusions, but it is unclear if the same flow velocity cut-offs can be applied to the Iranian population. We aimed to evaluate baseline TCD findings in Iranian children with SCD and no prior strokes. METHODS: Children with genetically confirmed SCD (Arabian haplotype, homozygote) and without SCD (controls) were prospectively recruited from pediatric outpatient clinic over a period of 9 months. We performed TCD in both groups to determine flow velocities in the middle cerebral (MCA) and terminal internal carotid arteries (TICA). RESULTS: Of 74 screened children, 60 met the inclusion/exclusion criteria (62% female; mean age 10±4 years). Baseline characteristics did not differ between the cases and controls, except hemoglobin (Hb) which was significantly lower in the SCD group (P<0.001). The right MCA TAMM (Time Averaged Maximum Mean) was significantly higher than in controls (125+5.52 cm/s vs. 92.5+1.63 cm/s, P<0.001). Left MCA did not show differences. The TICA TAMM was also different between cases and controls (P<0.05). CONCLUSIONS: Among Iranian children with asymptomatic SCD and without receiving recent transfusion TCD velocities are higher as compared to healthy controls but appear much lower than those observed in STOP (Stroke Prevention Trial in Sickle Cell Anemia) studies. We hypothesize that some children at high risk may be present with velocities lower than 170-200 cm/s thresholds. A prospective validation of ethnicity-specific prognostic criteria is warranted.

Zonisamide versus topiramate in migraine prophylaxis: a double-blind randomized clinical trial.

BACKGROUND: Topiramate is an antiepileptic drug that has been approved for migraine prophylaxis. Despite appropriate efficacy for migraine prophylaxis, some patients cannot tolerate its adverse effects. The aim of this study was to compare the efficacy of zonisamide, another antiepileptic drug, with topiramate in decreasing the frequency and severity of migraine attacks to determine whether it could be used as an alternative for noncompliant patients to topiramate. METHODS: Eighty patients, recruited from referred migraineurs to our neurology clinic, who met the diagnosis and inclusion criteria were allocated randomly to group A (50-mg/d zonisamide, gradually titrated up to 200 mg/d) and group B (25-mg/d topiramate, gradually titrated up to 100 mg/d). Each patient was followed for 12 weeks and was assessed at entrance, in the fourth week and twelfth week for frequency of attacks, headache severity, need for acute medication, migraine disability assessment score, and adverse effects. A P < 0.05 was considered as the level of significant difference in all tests. RESULTS: Both drugs caused a significant decrease in frequency, severity, need for acute medication in migraine attacks, and migraine disability assessment score (P < 0.05). Except headache severity that was reduced significantly better by zonisamide (P < 0.008), there were no significant difference between the 2 groups in other items. Except for 2 cases of intolerable paresthesia, both drugs were tolerated well during the study. CONCLUSION: Our results indicated that zonisamide is as effective as topiramate in migraine prophylaxis and can be considered as an alternative treatment when topiramate is not tolerated well.

The effect of NeuroAiD™ (MLC601) on cerebral blood flow velocity in subjects' post brain infarct in the middle cerebral artery territory.

BACKGROUND: Stroke is the third common cause of mortality and the most common cause of morbidity in adults. MLC601 (NeuroAiD™) is a treatment indicated for post stroke recovery. An increase of impaired cerebral blood flow may be an important parameter for recovery processes. The aim of this study was to investigate the effect of MLC601 on cerebral blood flow velocity as an indirect evidence of cerebral blood flow increase in post stroke subjects. METHODS: This is a double-blinded, placebo controlled, randomized study of 80 subjects included within a week of stroke onset. All subjects were given either MLC601 or placebo, 4 capsules, 3 times a day for 3 months. Cerebral blood flow within the middle cerebral artery, with blood flow velocity measured by transcranial Doppler (TCD), and Barthel index was assessed at baseline and at 3 months. RESULTS: The mean change in cerebral blood flow velocity in the MLC601 treatment group (15.9) was significantly increased (p=0.009) compared to the placebo group (9.6). Subjects in the treatment group also showed a significant difference in the mean rank of modified ranking scale (p<0.001) and mean change of the Barthel Index: 36 vs. 29 in the placebo group (p<0.001). CONCLUSION: This is the first study suggesting that treatment with MLC601 may increase cerebral blood flow in stroke subjects. This may be mediated by an effect on stimulating microcirculation, an important process contributing to neuroplasticity in the central nervous system. This effect on cerebral blood flow may be associated with improvement in measures of functional recovery.

Simple formulas for screening abnormal blood pressure in children and adolescents.

Childhood hypertension has been extensively focused on in the past decades because of its increasing incidence, which is related to physicians' awareness and the increasing number of obese children. Age, gender, and body size are the main determinants of blood pressure in children. The revised childhood blood pressure tables of the National High Blood Pressure Education Program are a prerequisite for classification of childhood hypertension. Although these tables provide a reasonable basis, they are intricate and height percentile is needed for final diagnosis. Many attempts have been done to decrease such complexity. We present new formulas that are concise and memorable, and will help physicians to screen prehypertensive and hypertensive pediatric patients.

Multicystic dysplastic kidney in association with congenital ichthyosiform erythroderma.

Multicystic dysplastic kidney is a noninherited congenital disease. Association of this disease with abnormalities of various organs is common. We, however, report a rare case of multicystic dysplastic kidney associated with congenital ichthyosiform erythroderma in an infant. Different developmental origins of the skin and the kidney can explain the scarcity of concurrent congenital skin and kidney abnormalities. Nonetheless, the development of both organs depends on mesenchyme-epithelial interactions for inductive signaling. It seems defects in the production of signaling molecules can explain such an association.