A Long-term Follow-up Study Of Heroin Spongiform Leukoencephalopathy

Background:Heroin spongiform leukoencephalopathy (HSLE), a rare kind of central nervous system leukoencephalopathy occurs in the crowd of heroin addicts, has an overall incidence of0.32%reported in the literature. HSLE was firstly discovered by the Wolters EC in the Netherlands, Amsterdam in1982. From then on, a few cases were reported in Europe, the U.S. and Taiwan. In China, HSLE was firstly reported in March,2000by Lu Bingxun, etc.Owing to its rarity occurs in the heroin addicts’ crowd, HSLE is not mentioned in the teaching materials or described in the monograph. Therefore, cases are rare and difficult to collect. Except the reports from the Netherlands (1982) and our research group, the rests are of individual. For lack of sufficient study, coupled with the limited level of technology and other conditions, we failed to conduct in-depth clinical studies.With the advancement of science and technology, medical imaging technology has got rapid development which provides a good condition for the in-depth examination of disease and helps us to understand the disease.Until now, there are no long-term follow-up or studies of large cases on HSLE. We are still unclear about the long-term prognosis, the neurological recovery and the prognosis of iconography. It is insufficient to understand the disease and evaluate the efficacy. However, we have the largest case in the world which provides a good learning chance for the long-term follow-up study and deepens our understanding and awareness.Objective:By summarizing various of findings from clinical studies and iconography with13years of follow-up belong to HSLE patients, this study goes deep into the analysis about clinic, imaging characteristics and prognosis, and provides a very important basis for people to recognize the disease.Materials and Methods:1.DataIn Neurology, Nanfang Hospital, from March2000to August2008,50patients diagnosed of HSLE, including40cases of inpatient,10cases of outpatient and epidemiological investigation of the patient.2. The methodGeneral Data Collection:Through a retrospective chart review of all patients’ records, we collected demographic data, including gender, age, birthplace, the incidence areas, drug time, drug use, drug quantity, the number of drug treatment, past history of other drug use, family genetic history and other basic information; patients’ clinical symptoms, signs and other information were also recorded.Laboratory data collection:The collection of cerebrospinal fluid routine biochemical test results of patients; virology test results:human immunodeficiency virus (HIV), Epstein-Barr virus (EBV), herpes simplex virus (HSV), cytomegalovirus (CMV); bacteriology test results:Treponema pallidum, Mycobacterium tuberculosis, toxoplasmosis, etc; blood biochemistry, urine morphine test results.Imaging data collection:Reviewed the patients’ imaging data, collected the information of head CT, MRI, enhanced MRI, MRA, DWI, MRS examination results, records lesions involving the location, extent, changes in the characteristics of the signal, intracranial vascular conditions, spectral characteristics, etc.Biopsy data collection:Records pathological findings at autopsy or brain tissue biopsy patients.Long-term follow-up:The follow-up questionnaire and physical examination was finished with an unified examination standard in a prescribed time. The follow-up survey questionnaire, self-designed scale of major neurological deficiency situation and results of iconography changes were recorded. The follow-up time were before treatment, the treatment after1month,6months,1year,2years,3years,5years,10years and13years.3. Statistical analysisSPSS13.0software was used for statistical analysis. Measurement data expresses as mean±standard deviation (x±s); Count data adopts frequency (n) or percentage (%). P<0.05is defined as statistically significant.Results:1. The results of general informationAmong the50patients,45are males and5are females. Ages from20to46years old, the mean age is29.6±3.7. In2000, we treated26cases,10from the Chaoyang District, Shantou City, Guangdong Province; In2004, we treated10cases,5from Guangzhou, Guangdong Province. All patients had a history of inhaling heroin, the shortest time is1year, the longest is up to10years, the mean month is 32.2±16.5. The daily drug range is0.5g to4.0g. Among the50,24patients are both inhaling heroin and intravenous heroin.38patients had a history of treatment before the onset. However,24patients developed the disease2-14days after the drug treatment,10cases1-2months,3cases3-4months and1case six months. There were3cases accepted detoxification treatment, but the process further aggravate the condition. Different treatments were used in different patients, among which10cases adopted "cold turkey method" detoxification, and the rests adopted drugs (such as methadone, nitrazepam, etc.) detoxification.15cases of drug treatment were in the drug rehabilitation center,20cases in hospitals or private clinics,6self-detoxification cases at home. All patients had no other history of drug use and family heredity.2. The clinical symptoms and signsClinical manifestations have similarities.47cases were acute onset,3cases were subacute onset. The illness will be at its peak in a few days to ten days and a few will last for more than a month. The first and prominent clinical manifestations were impaired cerebellar signs and symptoms, including cerebellar ataxia (unsteady gait, slow movement, staggering gait,even can not walk) and cerebellar language (poems like language, blasting language, intermittent language, slurred speech even can not speak); if progressed, the performance occurred such as the corticospinal tract, hemiplegic paralysis or quadriplegia, then the pathology is positive. Patients will also have a limb or head tremor of extrapyramidal manifestations. The serious conditions include disturbance of consciousness, decorticate state, spastic quadriplegia, akinetic mutism, convulsions and the disorder of autonomic nervous system. According to the patient’s state of consciousness, cerebellar signs and symptoms of pyramidal tract damage, we divided the disease into three phases, phase Ⅰ:cerebellar involvement (cerebellar symptoms and signs); phase Ⅱ:pyramidal tract involvement (cerebellum involvement of signs and symptoms associated with pyramidal tract damage symptoms); phase Ⅲ:disturbance of consciousness(coma, decorticate state, akinetic mutism, locked-in syndrome, etc.), combined pyramidal tract damage symptoms.3. Lab results8patients have a small amount increase of white blood cell count in the cerebrospinal fluid routine test, about1-10×106/L, the rests are normal; cerebrospinal fluid biochemistry indicators:5patients have mild elevation in protein levels, that is,0.46/0.48/0.50/0.56/0.60g/L, and the rests are normal. Glucose and sodium chloride of all patients are normal; The HIV, EBV, HSV, CMV, Treponema pallidum, Mycobacterium tuberculosis, toxoplasmosis antibodies of all patients are negative, together with the blood biochemical examinations and morphine in urine tests except one patient.4. Iconography resultsCT results:bilateral cerebellum, basal ganglia, subcortical white matter extensively, the symmetry of low-density lesions, especially on both sides of the midline cerebellum, clear boundary symmetry "butterfly-like" hypodense lesions are the most obvious; no mass effect.MRI results:bilateral cerebellar hemispheres, posterior limb of internal capsule, the splenium of the corpus callosum, cerebral hemisphere frontal, temporal, parietal, occipital or the brain stem white matter, widely symmetrical abnormal signal changes showed low signal on T1WI, high signal on T2WI, FLAIR sequence showed high signal changes slightly reduced compared with T2WI. All patients’ cerebella were affected but the anterior limb of internal capsule and the cerebral cortex were not affected.Enhanced MRI results:4patients underwent MRI enhanced scan, there were no enhancing lesions.MRA results:8patients underwent MRA scans.4patients’MRA were normal;3patients’vascular branching reduced and the diameter got thin;1patient’s vascular branching reduced, running stiff, tube wall rough, uneven thickness, like "string-of-beads" pattern.DWI sequence results:8patients underwent diffusion-weighted imaging, the lesions showed high signal or bright high signal, the apparent diffusion coefficient (apparent diffusion coefficient, ADC) lower than the normal brain tissue.MRS Results:4patients underwent MRS examination, compared with normal brain tissue, the common feature is the lower levels of NAA;2cases the change of Cho content is not obvious,2cases the Cho content decreased;2cases the change of Cr content is not obvious,2cases the Cr content decreased.5. HistopathologyPathology results suggested that the pathological feature of the disease is white matter spongiform vacuolar change.6. Long-term follow-up resultsClinical prognosis:The patients’ muscle recovered early and completely, but the cerebellar symptoms slowly. The fastest muscle recovery was6months, muscle of about89.4%patients returned to normal in5years follow-up, about92.3%in10years follow-up, and about94.1%in13years follow-up. Most patients’cerebellar symptoms recovered quickly after one year. But it still took time. Of5years follow-up, the speech&walking of full recovery accounted for only44.7%,47.3%;10-year follow-up about53.8%,61.5%;13-year follow-up about58.8%,70.5%. In addition,5of the7patients died in the three phases were.Imaging prognosis:intracranial lesions could be reduced according to the treatment and the improvement of the disease. But there is no significant correlation with the clinical symptoms and signs recovery. The time of the signal faded of MRI lesions is later than clinical signs and symptoms recovery, may even exist for a long time, lesions on DWI imaging sequence still showed high signal change. In addition, some patients had brain atrophy.Conclusions:(A) The epidemic characteristic of HSLE probably is local, small-scale outbreak;(B) The drug is a common cause of HSLE;(C) The most important pathology feature of HSLE is spongiform vacuolar degeneration in the white matter;(D) HSLE has clinical features, with three phases clinically;(E) HSLE imaging has the characteristics and is important to diagnosis;(F) The criterion of the diagnosis in HSLE is put forward/suggested;(G) There is no relativity between the disease progression of HSLE and the patient’s age, drug time, drug quantity, drug use;(H) Antioxidants and functional exercise is of great significance on the functional recovery of patients;(Ⅰ) Phase Ⅰ, Ⅱ patients have good prognosis, muscle recovered early and completely, but the cerebellar symptoms slowly; Phase Ⅲ patients with a poor prognosis;(J) Recovery of MRI is not according to the improvement of clinical signs and symptoms in patients.