Secondary Worsening Research Articles

Successful Treatment of Both Refractory Neuroleptic Malignant Syndrome and Subsequent Catatonia With Electroconvulsive Therapy in a Patient With Suspected Kufs Disease.

We describe a patient suffering from probable Kufs disease who developed a neuroleptic malignant syndrome (NMS) after use of an antipsychotic agent over some weeks during hospitalization due to neuropsychiatric symptoms. Transferred to the neurology department, the patient quickly developed catatonic features. She did not respond to usual medical treatment but did respond to electroconvulsive therapy (ECT). The patient worsened following a nosocomial SARS-CoV-2 infection but improved again during a second course of ECT. We discuss Kufs disease as a potential risk factor for NMS and address the link between NMS and catatonia as well as the indication for ECT in both disorders. We also discuss the impact of SARS-CoV-2 infection on the clinical outcome. We describe the long recovery process and the secondary worsening of the patient on a cognitive level.

Prospective evaluation of flow-regulated valves for idiopathic normal pressure hydrocephalus: 1-year results

ObjectiveOverdrainage and frequent reprogramming are common problems with programmable valves after ventriculoperitoneal shunt surgery for idiopathic normal pressure hydrocephalus (iNPH). Non-adjustable, flow-regulated valves offer a potential solution to these problems, but there is limited data on their efficacy. This study will evaluate neurological improvement and overdrainage rates within one year of treatment with a flow-regulated valve. Patients and MethodsThis prospective study analyzes 45 iNPH patients (median age: 73 years) treated with a flow-regulated valve. Clinical evaluations were performed at baseline, postoperatively, and at 3, 6, and 12 months after surgery. The primary efficacy endpoint was improvement of at least 5 points on the iNPH grading scale at follow-up. The safety endpoint was radiographic evidence of overdrainage. ResultsAll patients presented with gait disturbance, 35 (78 %) had cognitive impairment, and 35 (78 %) had urinary incontinence. The median duration of symptoms was 24 months. The total iNPH score improved in 33/41 (81 %) at 3 months, in 29/34 (85 %) at 6 months, and in 22/29 (64 %) at 12 months. Overall, 40/45 (89 %) patients had a significant improvement on the iNPH scale. Secondary worsening of symptoms after initial improvement was observed in 5 (11 %) patients. Overdrainage occurred in one patient (2 %) requiring surgical evacuation. ConclusionTreatment of iNPH patients with flow-regulated valves resulted in a good neurological outcome with minimal rates of overdrainage. These results are encouraging and justify the clinical use of these valve types.

"Pseudo"-Secondary Treatment Failure Explained via Disease Progression and Effective Botulinum Toxin Therapy: A Pilot Simulation Study.

The objective of this study was to provide evidence from a simple simulation. In patients with focal dystonia, an initial good response to botulinum neurotoxin (BoNT) injections followed by a secondary worsening does not necessarily arise from an antibody-induced secondary treatment failure (NAB-STF), but may stem from a "pseudo"-secondary treatment failure (PSEUDO-STF). The simulation of the outcome after BoNT long-term treatment was performed in four steps: 1. The effect of the first single BoNT injection (SI curve) was displayed as a 12-point graph, corresponding to the mean improvement from weeks 1 to 12. 2. The remaining severity of the dystonia during the nth injection cycle was calculated by subtracting the SI curve (weighted by the outcome after n - 1 cycles) from the outcome after week 12 of the (n - 1)th cycle. 3. A graph was chosen (the PRO curve), which represents the progression of the severity of the underlying disease during BoNT therapy. 4. The interaction between the outcome during the nth BoNT cycle and the PRO curve was determined. When the long-term outcome after n cycles of BoNT injections (applied every 3 months) was simulated as an interactive process, subtracting the effect of the first cycle (weighted by the outcome after n - 1 cycles) and adding the progression of the disease, an initial good improvement followed by secondary worsening results. This long-term outcome depends on the steepness of the progression and the duration of action of the first injection cycle. We termed this response behavior a "pseudo"-secondary treatment failure, as it can be compensated via a dose increase. A secondary worsening following an initial good response in BoNT therapy of focal dystonia might not necessarily indicate neutralizing antibody induction but could stem from a "PSEUDO"-STF (a combination of good response behavior and progression of the underlying disease). Thus, an adequate dose adaptation must be conducted before diagnosing a secondary treatment failure in the strict sense.

No Secondary Treatment Failure during Incobotulinumtoxin-A Long-Term Treatment Demonstrated by the Drawing of Disease Severity.

The aim of this study was to detect clinical hints regarding the development of secondary treatment failure (STF) in patients with focal dystonia who were exclusively treated with incobotulinumtoxin/A (incoBoNT/A). In total, 33 outpatients (26 with idiopathic cervical dystonia, 4 with Meige syndrome and 3 with other cranial dystonia) who were treated with repeated injections of incoBoNT/A for a mean period of 6.4 years without interruptions were recruited to draw the course of their disease severity (CoD) from the onset of symptoms to the onset of BoNT therapy (CoDB graph) and from the onset of BoNT therapy to recruitment (CoDA graph). At the time of recruitment, the patients assessed the change in severity as a percentage of the severity at the onset of BoNT therapy. Blood samples were taken to test the presence of neutralizing antibodies (NABs) using the mouse hemidiaphragm assay (MHDA). Patients reported an improvement of about 70% with respect to the mean. None of the patients tested positive for MHDA. Three different types of CoDB and three different types of CoDA graphs could be distinguished. The patients with different CoDB graphs reported different long-term outcomes, but there was no significant difference in long-term outcomes between patients with different CoDA graphs. None of the patients produced a CoDA graph with an initial improvement and a secondary worsening as a hint for the development of STF. A primary non-response was not observed in any of the patients. During long-term treatment with BoNT/A, NABs and/or STF may develop. However, in the present study on patients with incoBoNT/A long-term monotherapy, no hints for the development of NABs or STF could be detected, underlining the low antigenicity of incoBoNT/A.

Lessons about Botulinum Toxin A Therapy from Cervical Dystonia Patients Drawing the Course of Disease: A Pilot Study.

To compare the course of severity of cervical dystonia (CD) before and after long-term botulinum toxin (BoNT) therapy to detect indicators for a good or poor clinical outcome. A total of 74 outpatients with idiopathic CD who were continuously treated with BoNT and who had received at least three injections were consecutively recruited. Patients had to draw the course of severity of CD from the onset of symptoms until the onset of BoNT therapy (CoDB graph), and from the onset of BoNT therapy until the day of recruitment (CoDA graph) when they received their last BoNT injection. Mean duration of treatment was 9.6 years. Three main types of CoDB and four main types of CoDA graphs could be distinguished. The demographic and treatment-related data of the patients were extracted from the patients' charts. The best outcome was observed in those patients who had experienced a clear, rapid response in the beginning. These patients had been treated with the lowest doses and with a low number of BoNT preparation switches. The worst outcome was observed in those 17 patients who had drawn a good initial improvement, followed by a secondary worsening. These secondary nonresponders had been treated with the highest initial and actual doses and with frequent BoNT preparation switches. A total of 12 patients were primary nonresponders and did not experience any improvement at all. No relation between the CoDB and CoDA graphs could be detected. Primary and secondary nonresponses were observed for all three CoDB types. The use of initial high doses as a relevant risk factor for the later development of a secondary nonresponse was confirmed. Patients' drawings of their course of disease severity helps to easily detect "difficult to treat" primary and secondary nonresponders to BoNT on the one hand, but also to detect "golden responders" on the other hand.

COVID-19-associated encephalitis.

COVID-19 associated encephalitis has been reported in patients infected with SARS-CoV-2 since February 2020. The index case was reported in Japan, but since then, reports have emerged worldwide, with a global incidence rate of 0.215%, and regional incidence rates of up to 18%. While in the acute phase of infection, COVID-19-associated encephalitis can biologically mimic infectious limbic encephalitis, immune-inflammatory-mediated encephalopathy, herpes simplex encephalitis, produce hyperintensities in multiple regions of the brain, and mimic Alzheimer’s Disease. With a high mortality rate of 13.4%, COVID-19-associated encephalitis poses a significant burden on health systems and resources, requiring a combination diagnostic approach, supportive treatment regimens, and regular monitoring for secondary worsening of symptoms. COVID-19-associated encephalitis can emerge up to six weeks post-infection, and elevated risk levels can persist for six months post-infection. Despite emerging evidence and research, significant longitudinal research is required to ascertain the true prevalence and lifetime health risk of developing encephalitis following SARS-CoV-2 infection. This report aims to provide a summary of COVID-19 associated encephalitis.

Glial Fibrillary Acidic Protein (GFAP) Astrocytopathy Presenting as Mild Encephalopathy with Reversible Splenium Lesion

IntroductionAutoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is scarce and usually presents as meningoencephalomyelitis. Here, we offer the case of an atypical presentation of GFAP-astrocytopathy.Case PresentationWe report the case of a 26-year-old woman admitted to our neurology department for a 3-week progressive and worsening neurologic picture, with secondary worsening. Initial imaging showed a Mild Encephalitis with Reversible Splenium of corpus callosum lesion (MERS). Full infectious and autoimmune workup then revealed positivity of GFAP antibodies, leading us to diagnose GFAP astrocytopathy.DiscussionOur case is the first reported association between MERS and GFAP astrocytopathy in an adult patient. Clinical presentation of GFAP astrocytopathy usually includes various neurologic symptoms and can lead to misdiagnosis.

Secondary Worsening Following DYT1 Dystonia Deep Brain Stimulation: A Multi-country Cohort.

Objective: To reveal clinical characteristics of suboptimal responses to deep brain stimulation (DBS) in a multi-country DYT1 dystonia cohort.Methods: In this multi-country multi-center retrospective study, we analyzed the clinical data of DYT1 patients who experienced suboptimal responses to DBS defined as <30% improvement in dystonia scales at the last follow-up compared with baseline. We used a literature-driven historical cohort of 112 DYT1 patients for comparison.Results: Approximately 8% of our study cohort (11 out of 132) experienced suboptimal responses to DBS. Compared with the historical cohort, the multi-country cohort with suboptimal responses had a significantly younger age at onset (mean, 7.0 vs. 8.4 years; p = 0.025) and younger age at DBS (mean, 12.0 vs. 18.6 years; p = 0.019). Additionally, cranial involvement was more common in the multi-country cohort (before DBS, 64% vs. 45%, p = 0.074; before or after DBS, 91% vs. 47%, p = 0.001). Mean motor improvement at the last follow-up from baseline were 0% and 66% for the multi-country and historical cohorts, respectively. All 11 patients of the multi-country cohort had generalization of dystonia within 2.5 years after disease onset. All patients experienced dystonia improvement of >30% postoperatively; however, secondary worsening of dystonia commenced between 6 months and 3 years following DBS. The improvement at the last follow-up was less than 30% despite optimally-placed leads, a trial of multiple programming settings, and additional DBS surgeries in all patients. The on-/off-stimulation comparison at the long-term follow-up demonstrated beneficial effects of DBS despite missing the threshold of 30% improvement over baseline.Conclusion: Approximately 8% of patients represent a more aggressive phenotype of DYT1 dystonia characterized by younger age at onset, faster disease progression, and cranial involvement, which seems to be associated with long-term suboptimal responses to DBS (e.g., secondary worsening). This information could be useful for both clinicians and patients in clinical decision making and patient counseling before and following DBS implantations. Patients with this phenotype may have different neuroplasticity, neurogenetics, or possibly distinct neurophysiology.

COVID-19: don't neglect antimicrobial stewardship principles!

COVID-19: don't neglect antimicrobial stewardship principles!

Bacteriologically Confirmed Neuromeningeal Tuberculosis at the Hubert Koutoukou Maga National Hospital and University Center in Cotonou: About Two Cases Study and a Review of the Literature

Introduction: Tuberculosis remains a major public health problem. The damage to the central nervous system is severe. We reported here two cases. Clinical Case 1: A 37-year-old female patient, naively Human Immunodeficiency Virus1 (HIV1)-positive with antiretroviral (ARV) treatment, hospitalized in the Internal Medicine department for altered consciousness in a febrile context. The clinical examination at admission noted a meningeal syndrome. Cytological analysis of the cerebrospinal fluid (CSF) revealed lymphocytic meningitis with 98% lymphocytes for 3634 leukocytes. CSF polymerase chain reaction (PCR) detected Mycobacterium tuberculosis DNA. She was put on anti-tuberculosis treatment. The immediate course was favourable, but a secondary worsening of the clinical picture was the cause of his death. Clinical Case 2: A 34-year-old male patient, naively HIV1-positive with ARV treatment. He is hospitalized in the Multi-Purpose Anaesthesia and Resuscitation Department of the CNHU HKM for altered consciousness in a feverish context. The clinical examination noted a meningeal syndrome. The cytological analysis of the CSF noted 184 leukocytes for 99% lymphocytes. The CSF PCR identified the DNA of Mycobacterium tuberculosis. He was put on anti-tuberculosis treatment. The evolution was marked by his death. Conclusion: The neuromeningeal localization of tuberculosis is a poor prognosis. Co-infection with HIV remains a potential deadly combination.

Confirming the Brain Death and the Nurse’s Tasks in the Care of Potential Organ Donors and Their Families

Introduction. Transplantology is the youngest area of medicine dealing with organ transplantation that is considered to be the most difficult.Aim. The aim of the work is to analyse the nurse’s tasks in the care of the organ donor after confirming brain death and propagate the idea of transplantology.Case Report. A 52-year-old patient admitted to the hospital at the neurological department after a craniocerebral trauma. Computed tomography of the head showed brain contusion, fractures of the bones of the skull cover, the presence of a small amount of air in the cranial cavity. Immediately after admission, the patient was tangled, conscious, reluctant to answer questions, without paresis and a short-term seizure. Anti-oedema and anti-epileptic treatment was implemented in the neurosurgery department. After starting treatment, there was a temporary improvement, followed by a secondary worsening of brain and brain stem failure with deep cerebral coma. The patient was referred for further treatment in the Intensive Care Unit.Discussion. Organ transplantation involves collecting them from the donor and implanting them into the recipient. The donor can be either a living person (when it comes to paired organs or fragment of the liver as well as the tissues and cells) or the deceased person, who during their life did not express objection to organ donation after their death. The major principle in this case is the pronouncement of brain death, i.e. confirmation of patient’s death resulting in changing the therapeutic goals.Conclusions. Transplantology is an interdisciplinary field of medicine, the success of which relies on the cooperation of many professionals. The nurse takes an active part in the team’s work starting from the donor’s organs eligibility, through transplantation, to the care of the patient after the transplantation. The nurse also participates in building up an atmosphere favourable for good relations with the potential donor’s family. (JNNN 2019;8(3):124–132)

Abstract TP542: EEG Detection of Secondary Worsening of Neuronal Function in Malignant MCA Infarction: Development of a Tool to Identify Patients for Decompressive Hemicraniectomy

Hemicraniectomy (HC) improves mortality in Malignant Middle cerebral artery Infarctions (MMI), but patient selection and optimal timing for HC remains unclear. A continuous method to monitor for the risk and development of herniation from infarction would allow a better selection of patients for HC We hypothesized that certain EEG features reflective of worsening mass effect will be easier to detect on quantitative EEG (qEEG) analysis trends We studied qEEG trends before, during clinical deterioration (drop in GCS by at least 3 points) and after administration of osmotherapy. qEEG trends included rhythmicity spectra 0-25 Hz (scale 0- 2uV/Hz), Color Density Power Spectra (CSA) 0-20Hz (scale 0-2uV/Hz), amplitude integrated EEG (aEEG): 0-100uV and VsRhythmicity spectrogram 1 - 25 Hz (-3-3 Zscore) Trends demonstrated bilateral loss of power on beta and alpha frequencies and increase in theta preceded clinical deterioration by approximately 1 hour (left &gt; right). Patient2 subsequently had a robust theta power increase (+z score, red) in left &gt; right hemisphere which coincide with clinical deterioration on vsRhythmmicity Spectrogram. Also, there was a decreased of fast and slow frequencies bands on rhythmicity spectrogram and CSA with a diffuse attenuation outlined by aEEG (Left &gt; right). Following osmotherapy gradual improvement in all frequencies is seen but with an incomplete recovery in patient1 with lower alpha and theta power on right posterior and anterior quadrants suggested ongoing uncal and sub-falcine herniation, later confirmed on imaging Changes on qEEG reflecting impaired perfusion during acute herniation can manifest as decreased power in all frequency bands of varying severity prior to clinical deterioration. These changes can be completely or partially reversed with osmotherapy. Partial EEG response to osmotherapy may represent a potential sign of patients who will fail medical management and need DC. qEEG may be a helpful tool in HC patient selection

New evidence for oxetorone toxicity

Context: Oxetorone is a serotonin antagonist antimigraine drug but literature relating to its toxic properties is poor. The aim of this study is to describe the toxicological profile of oxetorone and to highlight any relationship between clinical and analytical findings.Materials and methods: This is a retrospective and observational study of cases exposure to oxetorone, reported to the Angers Poison and Toxicovigilance Centre between January 2002 and May 2016. Severity was assessed using the Poisoning Severity Score (PSS). Cases where data were incomplete, where oxetorone was deemed not accountable, where clinical signs were linked mainly to a co-ingested drug or where the plasma concentration of oxetorone was negative were all excluded.Results: We included 43 cases of exposure, 31 of whom were suicide attempts. The assumed ingested dose (60–3600 mg) was correlated to severity (rs = 0.45, p = 0.01). Symptoms of moderate severity (PSS2 = drowsiness, hypertonia, myosis, convulsions, arterial hypotension, QRS widening, QTc prolongation) were observed following ingestion of more than 600 mg of oxetorone (median dose =1200 mg) and severe symptoms (PSS 3 = coma, convulsions, QTc prolongation, QRS widening, ventricular tachycardia, arterial hypotension, cardiogenic shock) were observed starting from 1800 mg (median dose =2700 mg). In four cases, a secondary worsening of symptoms 10–48 h following ingestion was observed. Plasma oxetorone was measured in four patients. Severe symptoms were observed in the event of a concentration over 0.3 mg/L and the highest measured serum oxetorone level was delayed by 20–48 h following the ingestion for two cases.Conclusions: Several clinical and paraclinical parameters strongly point towards membrane-stabilising properties of the molecule and the risk of a delayed occurrence of symptoms or a secondary worsening.

Answer to the Letter to the Editor of J.M. Duart Clemente et al. concerning “multilevel oblique corpectomy for cervical spondylotic myelopathy preserves segmental motion” by AG Chacko, M Joseph, MK Turel, K Prabhu, RT Daniel, KS Jacob (2012) Eur Spine J. 2012;21(7):1360–1367

We thank J.M. Duart Clemente et al. for their interest in our article and raising important issues. Interestingly, the incidence of preoperative neck pain was low in our series despite this being a younger cohort of patients without degenerated and fused spines. In addition, neck pain was not a complaint noted during the follow-up period though we have not presented this in the results. We agree that the main goal of surgery is decompression for neurological improvement and not motion preservation. Ours was a unique group of younger patients with soft discs that stands in contrast to the older set of patients with degenerated and largely fused spines reported in Western series [1]. Having performed the oblique corpectomy with good outcomes, we noted the preservation of motion in the short term as a secondary finding that has not been reported previously with this technique. We have also documented a reduction in cervical motion with longer follow-up indicating that the body tends to fuse the spine with production of anterior osteophytes in this relentlessly progressive degenerative disease [2]. Furthermore, the analysis of data from our consecutive series of 153 patients demonstrated that the neurological function and thereby functional outcome was markedly improved following oblique corpectomy. This improved status remained without secondary worsening on long-term follow-up [3]. The technique of oblique corpectomy ensures the removal of the entire posterior surfaces of the affected vertebrae compressing the cord at presentation. The subsequent “cervicoarthrosis” that could reform on the long term are predominantly at the anterior surfaces of the vertebrae and cannot, therefore, endanger the decompressed spinal cord. This would explain the lack of progressive neurological deterioration at least due to a compressive element at the segments treated. We agree wholeheartedly that although motion preservation is not the primary objective of this surgery, we could avoid or at least retard the development of adjacent segment disease. Long-term follow-up is, of course, mandatory to ensure that these patients do not develop progressive kyphosis or adjacent segment disease.

A very early neurological improvement after intravenous thrombolysis for acute cerebral ischaemia does not necessarily predict a favourable outcome

In patients treated by intravenous (i.v.) thrombolytic therapy for cerebral ischaemia, a very early neurological improvement (VENI) [National Institutes of Health Stroke Scale score (NIHSSS) 0, or early improvement ≥5 points], predicts a favourable outcome. VENI patients are usually excluded from trials testing complementary strategies, but a few of them have bad outcomes. To determine why VENI patients may have bad outcomes, we analysed the reasons for bad outcomes [modified Rankin Scale (mRS) score 2-6 at 3months] in consecutive VENI patients. Of 365 consecutive patients with a pre-stroke mRS 0-1 (185 men, median age 69years, median NIHSSS 12, median onset-to-needle time 147min), 71 (19.5%) had VENI. They were more likely to have had recent transient ischaemic attacks (OR 3.64, 95% CI 1.08-12.27), higher baseline NIHSSS (median 14 vs. 11, p=0.003) and shorter onset-to-needle times (median 135min vs. 151, p=0.01), and they were less likely to develop pneumonia (OR 0.27, 95% CI 0.09-0.76) or malignant infarction (p=0.045). In the 21 VENI patients (29.6%) with a mRS 2-6 at 3-months, bad outcomes were due to the residual deficit in 14, secondary worsening of ischaemia in 4, intracranial haemorrhage in 2, and death from cancer in 1. One-third of VENI patients have bad outcomes, due to the residual neurological deficit in most of them. This finding suggests that VENI patients who still have a significant neurological deficit 1h after thrombolysis should not be excluded from trials testing complementary strategies.

Abstract 2247: A Very Early Neurological Improvement After Intravenous Thrombolysis For Acute Cerebral Ischemia Does Not Necessarily Predict A Favorable Outcome.

Background: in patients treated by intravenous (i.v.) thrombolytic therapy after cerebral ischemia, a very early neurological improvement (VENI) (National Institutes of Health Stroke Scale score [NIHSSS] 0, or early improvement &gt;5 points), predicts a favorable outcome. VENI patients are therefore usually excluded from trials testing complementary strategies. However, a few of them have bad outcomes. Objective: to determine why VENI patients may have bad outcomes Methods: we analyzed the reasons for bad outcomes (modified Rankin scale [mRS] score 2 to 6 at month-3) in consecutive VENI patients. Results: of 365 consecutive patients with a pre-stroke mRS 0-1 (185 men; median age 69 years; median NIHSSS 12; median onset-to-needle time 147 min), 71 (19.5%) had VENI. They were more likely to have had recent transient ischemic attacks (OR: 3.64; 95% CI: 1.08-12.27), higher baseline NIHSSS (median 14 vs. 11; p=0.003), and shorter onset-to-needle times (median 135 min vs. 151; p=0.01), and less likely to develop pneumonia (OR: 0.27; 95% CI: 0.09-0.76) or malignant infarction (p=0.045). In the 21 VENI patients (29.6%) with a mRS 2 to 6 at month-3 , bad outcomes were due to the residual deficit in 14, secondary worsening of ischemia in 4, intracranial hemorrhage in 2, and death from cancer in 1. Conclusion: one-third of VENI patients have bad outcomes, due to the residual neurological deficit in most of them. This finding suggests that VENI patients who still have a significant neurological deficit one hour after thrombolysis should not be excluded from trials testing complementary strategies.

Immunological Manifestations in Paraphenylene Diamine Poisoning

Objective: Our aim is to establish the immunologic profile of PPD-intoxicated persons based on monitoring of the inflammatory reaction. Methods and patients: A prospective study of 21 patients hospitalized in a medical ICU with PPD intoxication during 2010. A follow-up of demographic, clinical, paraclinical, therapeutic and evolutive parameters as well as evaluation of the scores of gravity (SAPS II, APACHE II, OSF) was carried out in all our patients, and an inflammatory check-up (white blood cell, Creactive protein, C3 and C4 fractions of complement and lymphocyte subpopulations CD3, CD4, CD8 and CD19) was realized for all patients. The kinetic of these parameters was compared with clinical and paraclinical evolution. Results: The monitoring of the inflammatory reaction in our patients shows an evolution at three times for this reaction, with the first time of inflammatory stress during the first 3 days after the intoxication characterized by a relative immunodepression, the second time from the third day when the rhabdomyolysis exerts its pro-inflammatory power and the third time (from the sixth day) corresponds to the immunomodulative action of PPD and to its oxidative metabolism. It’s a systemic and specific inflammatory reaction to a cytotoxic cell support, which would explain the secondary worsening of the clinical and paraclinical parameters of our patients (hemodynamic shock, multivisceral failure, etc.). Conclusion: It seems that the immunological aspect may present the answer to several questions that rhabdomyolysis alone could not answer during PPD-poisoning. This study tried to establish a first immunologic profile of PPD-intoxicated persons, and to correlate it with their evolution.

Searching for prognostic variables for secondary worsening after ischaemic stroke

Secondary worsening of stroke symptoms is described in 13-37% of stroke patients, but the exact mechanism of this phenomenon remains unclear. The aim of this study is to find prognostic variables in correlation to secondary worsening of stroke symptoms in patients with lacunar or cortical strokes. In this prospective observational study we included all patients with ischaemic stroke; patients with transient ischaemic attack were excluded. Patients undergoing thrombolysis and becoming symptom-free after 24 h were still included in our analyses. Secondary worsening of stroke symptoms was defined as an increase of two or more points on the NIH Stroke Scale (NIHSS). The NIHSS score was assessed on admission, at discharge, and when patients had symptoms that indicated worsening of stroke. Applying univariate and multivariable analysis, we studied the relation between symptoms indicating secondary worsening of stroke and prognostic variables such as extreme nocturnal blood pressure falls (>20% of the average blood pressure), infection, diabetes mellitus, hypertension, smoking, dyslipidaemia, a history of cardiovascular or cerebrovascular disease and thrombolysis. This study included 202 patients with a mean age of 72 years, 48.8% were men and 43% had a lacunar stroke. Secondary worsening of stroke symptoms occurred in 13.5% of all patients, more often but not significantly (NS) after lacunar than cortical strokes (16.8 and 11.4%, respectively), and in patients with extreme nocturnal blood pressure falls versus without (15.6 and 11.8%, respectively (NS)). There was no significant relation between the analysed prognostic variables and secondary worsening of stroke symptoms. This study did not show significant correlation between several variables and secondary worsening of stroke symptoms in patients with recent ischaemic stroke.

Pyoderma gangrenosum cutanéomuqueux et systémique

Extracutaneous and mucosal involvement is rare in neutrophilic dermatoses. We report a case of cutaneous-mucosal and systemic pyoderma gangrenosum (PG) revealing myelodysplasic syndrome. A 56-year-old man was hospitalised for an inflammatory abdominal plaque with an ulcerated centre that appeared rapidly in a setting of fever of 40 degrees C, odynophagia, weight loss and arthritis of the ankle. Despite surgical abdominal repair and combined dual antibiotics, the patient remained febrile and the ulcer size continued to increase. The edges were raised, purple and necrotic. Examination revealed vegetative legions with a purple edge on the lower lip and tongue. Histological examination of the skin and mucosal biopsy samples was consistent with a diagnosis of PG. A chest-abdomen CT scan showed mesenteric panniculitis and interstitial lung disease. The bone marrow sample revealed an appearance of chronic myelomonocytic leukaemia with myelofibrosis and excessively high blast levels. Systemic corticosteroids rapidly resulted in apyrexia with healing of the cutaneous, mucosal and visceral lesions. The patient presented secondary worsening of his acute myeloid leukaemia type-IV requiring bone marrow rescue. Extracutaneous involvement in neutrophilic dermatoses is rare but takes a number of different forms. We report a case of a patient presenting multifocal PG with cutaneous, mucosal, joint, mesenteric and pulmonary involvement. Oral lesions seen in PG generally affect the palate and they are commonly associated with inflammatory intestinal diseases. Our case is original in terms of the inaugural character of the mucosal lesions, their burgeoning appearance and their location on the lips and tongue.

Juvenile rapid-onset dystonia parkinsonism due to a 'de novo' mutation in the ATP1A3 gene

We report the first juvenile patient with rapid onset dystonia parkinsonism with a 'de novo' mutation in the ATP1A3 gene. Dystonia developed abrupt on the left side of the body at the age of 9, a secondary acute worsening caused prominent dysarthria at the age of 15. A 'de novo' T613M missense mutation in the ATP1A3 gene was found. We conclude that rapid onset dystonia parkinsonism should be considered in patients with acute dysarthria and acute hemidystonia without evidence of structural or vascular abnormalities on magnetic resonance imaging, even in the absence of a positive family history.