Clinical and cerebrospinal fluid cytological observations of neuroleukopenia syndrome Behcet Disease is a systemic vasculitis of unknown etiology, probably related to infection-induced autoimmune response and neutrophil hyperfunction. NBS is a common complication of Behcet disease, with an incidence of 4%-49% reported in the literature and about 10% in our hospital. The clinical manifestations of NBS are diverse, generally with acute or subacute onset, and manifesting as a single focal or multifocal CNS lesion. RESULTS I. Clinical manifestations: There were 27 cases of neuroleptic-leukodystrophy syndrome, including 21 males and 6 females, aged 17-62 years, with a duration of 1 month to 22 years. Clinical manifestations: all had oral ulcers, 22 cases had external genital ulcers, 9 cases of ophthalmia, 7 cases of folliculitis-like rash, 9 cases of fever, 38-39°C, irregular fever. Neurological manifestations: all showed neurological involvement, and the time between onset (appearance of skin and mucosal symptoms) and appearance of neurological damage was 27 days to 20 years. Neurological symptoms had an acute onset in 19 cases, a subacute onset in 7 cases, and a chronic onset in 2 cases. Neurological manifestations: headache in 9 cases, hemiparesis in 8 cases, diplopia in 6 cases, hemianesthesia in 5 cases, impaired consciousness in 5 cases, aphasia in 3 cases, seizures in 3 cases, abnormal mental behavior and decreased intelligence in 6 cases, ataxia in 2 cases, choking cough, dysphagia, hoarseness in 2 cases, Parkinson’s syndrome in 1 case, paraplegia in 2 cases. Other system involvement: 4 cases of intestinal leukoaraiosis, 2 cases of combined superior vena cava syndrome, 4 cases of bilateral lower extremity deep vein thrombosis, 2 cases of pulmonary embolism, 1 case of combined psoriasis, and 1 case of abnormal bone marrow hyperplasia. Treatment and regression: 23 cases were treated with hormone therapy, oral prednisone 30-60 mg/d, including 2 cases of methylprednisolone shock therapy, 17 cases were treated with CTX, 1 case was treated with cyclophilin A, 1 case died, and the remaining patients showed significant improvement of neurological symptoms. Sixteen cases were followed up from 3 months to 3 years with stable disease. Neuroimaging: 18 cases of head CT, 15 cases did not show any abnormality, 3 cases of basal ganglia infarction, including 1 case of hemorrhagic infarction; 1 case of basal ganglia hemorrhage. MRI (magnetic resonance imaging) of the head was performed in 20 cases, with 16 cases of abnormalities, which were multiple medium to small lamellar long T1 low or low signal and long T2 high signal, distributed in the basal ganglia, brainstem, paraventricular white matter and thalamus, among which 8 cases were distributed bilaterally, and 9 cases of enhanced MR, all of which were enhanced. 2 cases of MR of the cervical spinal cord: enhanced lesions were seen. 3 cases of MRV, 1 case was consistent with superior sagittal sinus thrombosis. Laboratory tests: 7 cases of mildly elevated leukocytes in routine blood tests, with predominantly elevated neutrophils; 10 cases of increased hematocrit (28-85 mm/hour). All patients underwent a comprehensive immunoserum blood test, and all were negative for autoantibodies such as antinuclear antibody profile and antineutrophil cytoplasmic antibody, one was positive for HLA-B27, four had elevated serum immunoglobulin, and one was strongly positive for PPD test. 19 cases underwent lumbar puncture CSF examination: eight had elevated CSF pressure (210-400 mmH2O), 17 had elevated CSF protein (0.48-1.08 g/L), and 19 had elevated CSF protein (1.08 g/L). The CSF protein was elevated in 17 cases (0.48-1.08 g/L), the Ig synthesis rate was elevated in 2 cases, and the oligoclonal zone was positive in 1 case. 11 cases had elevated leukocytes (11-48×106/L). Bacteriological and virological examinations were performed in all patients, and there were no special findings. CSF cytology: 11 cases were examined by CSF cytology. 7 cases were lymphocyte-dominated inflammation, of which 6 cases were accompanied by mildly elevated neutrophil ratio, with neutrophil ratio of 5% to 10%; 3 cases were mixed lymphocyte-neutrophil-dominated inflammation with neutrophil ratio of 10% to 50%; 1 case was neutrophilic inflammation with neutrophil ratio of 80%. 10 Activated lymphocytes could be seen, and some of them were seen as plasma cells. In one patient, 2 lumbar punctures and CSF cytology were performed, the first time with mild lymphocytic inflammation with a neutrophil ratio of 1%, and a week later, CSF cytology was repeated: the inflammatory response was aggravated with 50% lymphocytes and 40% neutrophils, called mixed inflammation. The early typical lesions resemble leukocytoclastic vasculitis or neutrophilic vasculitis, and later lymphocytic vasculitis. Neurological damage in leukoaraiosis includes brain parenchymal involvement, meningeal involvement, and venous sinus thrombophlebitis. More than half of the CNS leukemias are purely cerebral parenchymal. The autopsy pathology of this case suggests that vasculitis mainly involves small vessels in the brain or brainstem, especially small veins, with ischemic changes such as cerebral infarction, cerebral softening and demyelination around the vessels. The main clinical manifestations of neuroleukopenia syndrome include: (1) meningeal involvement or meningitis, with headache as the main symptom, 9 cases in this group, accounting for 33.3%; literature reports account for 33.3%-85%, the degree is mild, there may be intracranial pressure increase performance, meningeal irritation signs may not be obvious. (2) Brainstem involvement, 10 cases in this group, 36.7% of this group, is the most common part of the brain parenchymal damage in leukoaraiosis, Akman-Demir et al. reported 162 cases of parenchymal damage NBS, 83 cases involved the brainstem, with more midbrain lesions, diplopia, eye movement disorders, medulla oblongata involvement manifested as ball palsy: choking, dysphagia, etc., often combined with long bundle involvement. (3) Thalamic involvement: mental abnormality and disorders of consciousness, mental retardation, aphasia. (4) White matter or cortical involvement of the brain, with lateral ventricular parietal white matter involvement common, limb hemiparesis, hemianesthesia, seizures, etc. The hippocampus may be one of the vulnerable sites. (5) Extrapyramidal involvement, manifesting as lateralized choreographic movements or Parkinson’s syndrome, may be related to pallidum or midbrain nigrostriatal involvement. (6) Cerebellar involvement, showing ataxia. (7) Spinal cord lesion, 2 cases in this group, showing paraplegia. (8) Intracranial venous sinus thrombosis, accounting for about 1/31~/5 of CNS damage, mainly manifested as acute cranial hypertension, only one case in this group was diagnosed with intracranial venous sinus thrombosis, which may be related to less head MRV or head DSA examination in this group. Neuroimaging changes of NBS are characteristic. The typical MRI presentation is: in the acute phase, the lesion is mainly in the basal ganglia, brainstem, mesencephalon and internal capsule, with a lamellar T1 low signal and T2 high signal, especially in T2, and the edema is more prominent; in the recovery phase or chronic phase, the original lesion is obviously reduced or even disappears completely, leaving atrophy of the posterior cranial fossa structures or very small softening foci, this imaging change indicates that the lesion in the acute phase is mainly small venous stasis and tissue edema. This imaging change indicates that the acute phase of the disease is dominated by small venous stasis and tissue edema, rather than arterial occlusion causing cerebral infarction. It has been suggested that the involvement of the basal ganglia, brainstem and internal capsule in leukoencephalopathy may be due to the lack of physiological anastomotic or collateral circulation in the venous circulation in these areas and the significant impairment of venous return after local venous involvement. Akman-Demir et al. reported elevated CSF protein or leukocytes in about 60% of NBS, of which 54% were neutrophil-dominant or mixed neutrophil-lymphocyte inflammation and 46% were lymphocyte-dominant. kidd et al. reported 18 cases of brainstem NBS, 17 with abnormal CSF, mainly with mild leukocytosis , lymphocyte predominant and, commonly, neutrophils (mean 9.5%). In 90.9% (10/11) of our cases, an elevated proportion of neutrophils was seen on CSF cytology, which is consistent with the literature. Some investigators have found that such cytological changes persist during the active phase of NBS. In addition, I observed one case of increased inflammatory response in the cerebrospinal fluid after lumbar puncture, which has not been reported similarly before. We speculate that the mechanism may be due to neutrophil hyperfunction in patients with leukoaraiosis, and that the local injury by lumbar puncture caused an excessive inflammatory response, as in the mechanism of the leukoaraiosis pinprick response. We believe that CSF neutrophilia in NBS is consistent with the pathological mechanism of neutrophilic vasculitis in this disease and is a mechanism-specific indicator that has some significance for the diagnosis of NBS. Such CSF cytological changes are rarely seen in inflammatory diseases of the brain parenchyma such as inflammatory demyelinating diseases of the central nervous system and viral encephalitis. In our clinical practice, the possibility of NBS is often considered when we encounter inflammatory encephalopathies with typical imaging changes and a mixed inflammatory CSF, and it is not uncommon to confirm the diagnosis of NBS by following the history of oral ulcers and other medical problems. On the other hand, as a secondary CNS vasculitis, NBS provides a clinical model for neurologists to understand CNS vasculitis, especially small venous vasculitis. Understanding its pathology, clinical, neuroimaging, and CSF cytologic features will help us to diagnose this disease.