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The slow-channel congenital myasthenic syndrome is an autosomal dominant neuromuscular disorder caused by mutations in different subunits of the acetylcholine receptor. Fluoxetine, a common antidepressant and long-lived open-channel blocker of acetylcholine receptor, has been reported to be beneficial in the slow-channel congenital myasthenic syndrome. Here we report a prospective open label study of fluoxetine treatment in some affected members of a Thai family with slow-channel congenital myasthenic syndrome caused by a novel p.Gly153Ala (c.518G C) mutation in CHRNA1 in the AChR α subunit. These patients showed significant clinical improvement following fluoxetine treatment but their respiratory function responded variably.

Summary Background The Thymectomy Trial in Non-Thymomatous Myasthenia Gravis Patients Receiving Prednisone (MGTX) showed that thymectomy combined with prednisone was superior to prednisone alone in improving clinical status as measured by the Quantitative Myasthenia Gravis (QMG) score in patients with generalised non-thymomatous myasthenia gravis at 3 years. We investigated the long-term effects of thymectomy up to 5 years on clinical status, medication requirements, and adverse events. Methods We did a rater-blinded 2-year extension study at 36 centres in 15 countries for all patients who completed the randomised controlled MGTX and were willing to participate. MGTX patients were aged 18 to 65 years at enrolment, had generalised non-thymomatous myasthenia gravis of less than 5 years' duration, had acetylcholine receptor antibody titres of 1·00 nmol/L or higher (or concentrations of 0·50–0·99 nmol/L if diagnosis was confirmed by positive edrophonium or abnormal repetitive nerve stimulation, or abnormal single fibre electromyography), had Myasthenia Gravis Foundation of America Clinical Classification Class II–IV disease, and were on optimal anticholinesterase therapy with or without oral corticosteroids. In MGTX, patients were randomly assigned (1:1) to either thymectomy plus prednisone or prednisone alone. All patients in both groups received oral prednisone at doses titrated up to 100 mg on alternate days until they achieved minimal manifestation status. The primary endpoints of the extension phase were the time-weighted means of the QMG score and alternate-day prednisone dose from month 0 to month 60. Analyses were by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00294658. It is closed to new participants, with follow-up completed. Findings Of the 111 patients who completed the 3-year MGTX, 68 (61%) entered the extension study between Sept 1, 2009, and Aug 26, 2015 (33 in the prednisone alone group and 35 in the prednisone plus thymectomy group). 50 (74%) patients completed the 60-month assessment, 24 in the prednisone alone group and 26 in the prednisone plus thymectomy group. At 5 years, patients in the thymectomy plus prednisone group had significantly lower time-weighted mean QMG scores (5·47 [SD 3·87] vs 9·34 [5·08]; p=0·0007) and mean alternate-day prednisone doses (24 mg [SD 21] vs 48 mg [29]; p=0·0002) than did those in the prednisone alone group. 14 (42%) of 33 patients in the prednisone group, and 12 (34%) of 35 in the thymectomy plus prednisone group, had at least one adverse event by month 60. No treatment-related deaths were reported during the extension phase. Interpretation At 5 years, thymectomy plus prednisone continues to confer benefits in patients with generalised non-thymomatous myasthenia gravis compared with prednisone alone. Although caution is appropriate when generalising our findings because of the small sample size of our study, they nevertheless provide further support for the benefits of thymectomy in patients with generalised non-thymomatous myasthenia gravis. Funding National Institutes of Health, National Institute of Neurological Disorders and Stroke.

Acetazolamide is commonly used as an empirical treatment for inherited periodic paralyses although some patients may develop deleterious effects. We report a 65 year-old man with hyperkalemic periodic paralysis and late-onset permanent weakness in association with the common T704M mutation in α-subunit, skeletal muscle voltage-gated sodium channel gene. He rapidly recovered from weakness after acetazolamide treatment. Magnetic resonance imaging of thighs comparing pre- and post-treatment revealed a significant increase in muscle bulk. The patient has been without any type of weakness for over 6 years. This data show the remarkable benefit of acetazolamide on permanent weakness of hyperkalemic periodic paralysis in association with the T704M mutation.

A small but variable subgroup of patients with myasthenia gravis (MG) who have antibodies to muscle-specific kinase (MuSKAb-MG) can present with distinct phenotypes and are often treatment-resistant. The prevalence, clinical phenotypes and outcomes of treatment of patients with MuSKAb-MG in Thailand were determined. Eight (16.3%) of the 49 patients with generalized MG who were negative for acetylcholine receptor antibodies (AChRAb) were positive for muscle-specific kinase antibodies. Most patients had predominant oculobulbar features and respiratory failure occurred in three. At follow up, three out of the seven patients who underwent thymectomy were in complete stable remission and four had improved and were on reduced immunosuppression medication, suggesting a possible benefit of thymectomy. © 2012 Elsevier Ltd. All rights reserved.

highlights The sensitivities of RNS, SFEMG and AChRAb in the diagnosis of MG were documented. SFEMG abnormality correlated with clinical phenotype and AChRAb seropositivity. Difference in severity between ocular and generalized MG was confirmed by SFEMG. SFEMG demonstrated difference in severity between seronegative and seropositive MG. abstract Objective: To determine the diagnostic sensitivity of repetitive nerve stimulation (RNS), single fiber elec- tromyography (SFEMG) and acetylcholine receptor antibody (AChRAb) in myasthenia gravis (MG), and to compare the degree of SFEMG abnormality between ocular and generalized MG and between seronega- tive and seropositive patients. Methods: The sensitivities of RNS, SFEMG and AChRAb were estimated. SFEMG abnormality was com- pared between ocular and generalized MG and between seronegative and seropositive patients. Results: Abnormal RNS, abnormal SFEMG and AChRAb were detected in 62%, 93% and 38% of 42 ocular, and 80%, 99% and 73% of 70 generalized cases, respectively. The degree of SFEMG abnormality was sig- nificantly greater in the generalized than ocular patients and was significantly greater in the seropositive than seronegative patients in both extensor digitorum communis and orbicularis oculi muscles. Conclusion: SFEMG is a very sensitive and useful test for MG. A correlation between SFEMG abnormality and clinical phenotype or severity and between SFEMG abnormality and AChRAb seropositivity was dem- onstrated. Significance: The sensitivities of RNS, SFEMG and AChRAb in the diagnosis of MG were documented. The differences in severity between the ocular and generalized MG and between the seronegative and sero- positive MG were confirmed and quantitatively determined by SFEMG.

Glioblastoma multiforme (GBM) often occurs in the supratentorial white matter including corpus callosum. However, spinal leptomeningeal metastasis in cases of supratentorial GBM has been reported to be rare and there is usually a long interval between the cerebral lesion and the spinal seeding. We report here a case of GBM at the corpus callosum and other parts of the brain with simultaneous manifestation of spinal leptomeningeal seeding. The patient exhibited an abnormal motor behavior of the left hand as mirror movement when the right hand was performing a unimanual task (diagonistic dyspraxia) which is a sign of lesion of the posterior part and splenium of the corpus callosum. There were also signs of peripheral nerve or nerve root involvement suggestive of spinal metastasis without any sensory symptoms. He died 3 months after the onset of the symptoms confirming the poor prognosis and short survival time in cases with spinal leptomeningeal metastasis reported previously. The cerebral GBM with spinal seeding was disclosed at autopsy.

The slow-channel congenital myasthenic syndrome (SCCMS) is an autosomal dominant neuromuscular disorder caused by mutations in different subunits of the acetylcholine receptor (AChR). We here report our clinical findings in three generation of a large Thai kinship suffering from a SCCMS and trace the disease to the p. Gly153Ser mutation in the AChR α subunit. The same mutation had previously been reported only in Caucasian families but not in Asian patients. The clinical features include ptosis, ophthalmoparesis, and weakness of the cervical and finger extensor muscles as well as marked intrafamily phenotypic heterogeneity.

Idiopathic hypertrophic cranial pachymeningitis is a rare chronic inflammatory process of unknown origin that can cause neurological deficits owing to thickening of the dura. Patients with this condition commonly present with cranial neuropathy accompanied by localized headache. The clinical features, neuroimaging findings, histopathological features and treatment outcomes for three patients with this condition are reported here. The first patient presented with subacute dull headache in the left temporal area followed by left abducens nerve palsy. The second patient suffered from a cranial nerve IX-XII lesion accompanied by an occipital headache and the third patient presented with left optic neuropathy and mild headache in the frontal area. In all patients, MRI of the brain revealed prominent dural thickening, and histopathological study of the dura revealed chronic inflammatory cell infiltration. Combined therapy with corticosteroid and immunosuppressive drugs was effective, resulting in almost complete resolution of the symptoms and signs, except for visual impairment in one patient.

Determine and compare the clinicopathological findings of cerebral aspergillosis with cerebral candidiasis.The medical records with cerebral aspergillosis and cerebral candidiasis in Ramathibodi Hospital between January 1997 and December 2008 were analyzed. The criterion for the diagnosis of cerebral aspergillosis and cerebral candidiasis was the evidence of fungal elements from histopathologic section. The age, gender neurological manifestations, duration of symptom, associated underlying disease, predisposing risk factor, laboratory data, extent of systemic organ involvement and treatment outcome were analyzed.The present study included cerebral aspergillosis (n = 41) and candidiasis (n = 15). There were 23 male and 33 female patients. The mean and median ages at diagnosis were 39.7 and 45 years, respectively (range, 1 month to 87 years). The clinical presentations included alteration of consciousness (69.6%), fever (60.7%), weakness of the extremity (14.3%), cranial nerve palsy (12.5%), headache (12.59%) and seizure (5.4%). One third of the cases had underlying hematologic malignancy. The cerebral aspergillosis and cerebral candidiasis were associated with corticosteroids treatment in 32.1%. The frequent associated sites of fungal infection included the lungs (73.2%), alimentary tract (33.9%) and sinonasal tract (19.6%).A diagnosis of cerebral aspergillosis and cerebral candidiasis requires a high index of suspicion especially in immunocompromised patients who presented with alteration of consciousness, fever, focal neurological deficit, headache, and seizure. The patients with cerebral aspergillosis and cerebral candidiasis manifest with similar clinicopathologic features. However, the sinonasal tract infection and abscess formation are more common in cerebral aspergillosis. Associated alimentary tract infection is commonly seen in cerebral candidiasis.

Oculopharyngeal muscular dystrophy (OPMD) is an inherited neuromuscular disease associated with a short trinucleotide repeat expansion in Exon 1 of the PABPN1 gene. OPMD is uncommon in East Asian populations, and there have been no previous reports of Thai patients. We studied clinical and molecular genetic features of six unrelated Thai patients with autosomal dominant OPMD. All patients had expansions of the guanine-cytosine-guanine (GCG) repeat ranging from three to seven additional repeats in the PABPN1 gene. Haplotype analysis showed that these mutations might have originated independently. Analysis of the size of the GCG repeat in the PABPN1 gene in 200 Thai control patients showed that 0.5% of the control subjects possessed (GCG)(7), thereby suggesting that the prevalence of autosomal recessive OPMD in the Thai population was approximately 1 in 160,000. In conclusion, our data suggest that OPMD in Thailand may be more common than previously thought.

Botulism is a rare presynaptic neuromuscular junction disorder caused by potent toxins produced by the anaerobic, spore-forming, Gram-positive bacterium Clostridium botulinum. Food-borne botulism is caused by the ingestion of foods contaminated with botulinum toxin. In March 2006, there was a large outbreak of food-borne botulism associated with the ingestion of home-canned bamboo shoots in Thailand. The survival analyses for respiratory failure in these patients were studied and are reported here.A prospective observational cohort study was conducted on this outbreak. The primary outcome of interest was the time to respiratory failure. The secondary outcome was the time to weaning off ventilator. The prognostic factors associated with respiratory failure and weaning off ventilator are presented.A total of 91 in-patients with baseline clinical characteristics were included. Most cases first presented with gastrointestinal symptoms followed by neurological symptoms, the most striking of which being difficulty in swallowing. Common clinical features included ptosis, ophthalmoplegia, proximal muscle weakness, pupillary abnormality, and respiratory failure. Forty-two patients developed respiratory failure requiring mechanical ventilation and the median duration on ventilator was 14 days. The median length of hospital stay for all patients was 13.5 days. Difficulty in breathing, moderate to severe ptosis, and dilated and fixed pupils were associated with respiratory failure. Among patients who were on ventilators, a short incubation period and pupillary abnormality were associated with a longer period of mechanical ventilation. All patients had antitoxin injection and there was no mortality in this outbreak.The history of difficult breathing and the findings of moderate to severe ptosis and pupillary abnormality were associated with severe illness and respiratory failure. A long incubation time was associated with a better prognosis. Although botulism is a potentially fatal disease, there was no mortality in this outbreak. All patients had antitoxin injection and good intensive care that resulted in good clinical outcomes.

We report a 69-year-old woman who presented with dyspnea, orthopnea, and acute renal failure. She also had proximal muscle weakness suggestive of muscle disease. Her symptoms were alleviated by induced dieresis, although there was high-serum creatine kinase. Investigations for any possible etiologies of rhabdomyolysis were all negative. An X-linked recessive muscle disease was highly suspicious in view of the fact that both of her sons had suffered from muscle disease and died of respiratory failure at the ages of 22 and 29, respectively. Her muscle biopsy showed mosaic pattern with dystrophin antibody against amino-terminal, carboxy-terminal, and rod domain. Her DNA study revealed heterozygous duplication at exon 1 to 6 of the dystrophin gene as well. Therefore, she is a manifesting carrier of dystrophinopathy who was first diagnosed in late adulthood with congestive heart failure, acute episode of spontaneous rhabdomyolysis, and acute renal failure.

Dysferlinopathy refers to a variety of autosomal recessive, skeletal muscle disorders due to the mutations of dysferlin-encoding gene, DYSF. It encompasses limb-girdle muscular dystrophy type 2B (LGMD2B), Miyoshi myopathy (MM), distal myopathy with anterior tibial onset (DMAT), isolated hyperCKemia, rigid spine syndrome and congenital muscular dystrophy. Herein, we report five Thai patients with distal myopathy due to dysferlinopathy including four MM and one DMAT patients. Muscle biopsy from one MM patient depicted numerous ring fibers which is an atypical finding in dysferlinopathy. Mutation analysis of DYSF revealed novel compound heterozygous mutations of p.Tyr309X and c.236+1G>T in two related MM patients, known homozygous mutations, p.Arg89X and p.Gln176X, in two MM patients and a heterozygous missense mutation, p.Arg555Trp, in a DMAT patient. Most of the previously reported DMAT patients were Hispanic. To the best of our knowledge, this is the first report of genetically confirmed patients with dysferlinopathy in Thailand.

Objective: An electrophysiological study can help to confirm the diagnosis of botulism. This study was aimed at validating a simple and reliable electrodiagnostic test and at correlating the findings with clinical severity. Methods: Pre- and post-exercise single supramaximal stimulations (SSSs) were performed in 63 patients with botulism. The sensitivity and specificity of amplitude of compound muscle action potential (CMAP) and percentage increment (PI) of SSS were determined. These two parameters were then correlated with respiratory failure. The relationship between the amplitude of CMAP and PI was also studied. Results: SSS with a PI of 25% showed a sensitivity of 95.2% and a specificity of 100% in association with botulism. The area under the receiver operating characteristic (ROC) curve of CMAP and PI was associated with the respiratory failure by 0.7 and 0.6, respectively. An inverse relationship between the amplitude of CMAP and PI was also demonstrated. Conclusions: SSS is sensitive and specific in the diagnosis of botulism. There was some correlation of the findings with clinical severity. The inverse relationship between the amplitude of CMAP and PI reflects the pathophysiology of this disorder. Significance: This study has validated SSS as being a simple and reliable electrodiagnostic test for botulism.

Repetitive nerve stimulation (RNS) plays an important role in the diagnosis of myasthenia gravis (MG). Technically, this test can be more easily performed on distal muscles than proximal muscles. On the other hand, proximal muscles have been shown to be more easily fatigued or more sensitive than the distal ones.Evaluate the relative fatigability of different muscles in response to RNS in ocular and generalized MG patients.Two hundred patients with 44 ocular MG and 156 generalized MG were studied The relative fatigability of each muscle was calculated as percentage of cases with abnormal response. A decrement of 10% or more of the amplitude of the compound muscle action potentials was considered abnormal.The cases with abnormal response of adductor digiti minimi, anconeus, trapezius, nasalis and orbicularis oculi were 17%, 50%, 55%, 62%, 66% in ocular MG and 53%, 77%, 79%, 85%, 79% in generalized MG respectively. These results showed that in generalized MG the response in all the muscles was more frequently abnormal and was fatigable in a more comparable degree, whereas in ocular MG, the facial muscles were more often abnormal than the limb muscles.The abnormal response because of fatigability was more widespread in generalized MG whereas facial muscles were relatively more sensitive in ocular MG. This finding may be useful for the selection of the muscles to be tested in RNS especially in ocular MG.

Polyneuropathy from thiamin deficiency can occur in persons who consume a diet consisting mainly of polished rice with low protein and thiamin content in the setting of excessive physical activity or hypermetabolic states. The authors report here a 17-year-old fisherman who presented with a 3-month history of symptoms and signs consistent with polyneuropathy. There were also clinical features of thyrotoxicosis which was confirmed by thyroid function test. His dietary intake consisted mainly of polished rice and fish both of which contain a small amount of thiamin. This could not cope with his hypermetabolic condition from thyrotoxicosis resulting in thiamin deficiency with polyneuropathy.

POEMS (polyneuropathy, organomegaly, endocrinopathy, M protein and skin changes) syndrome is a multisystem disorder associated with plasma cell dyscrasia. Other clinical signs include clubbing of the fingers, edema, papilledema etc. Although papilledema and increased intracranial pressure are common features, their causes or pathophysiology have been uncertain. The authors report here a 16-year-old Thai patient with these features who also suffered from venous sinus thrombosis and visual failure which have never been reported before. The former is considered to be one of the possible causes of the intracranial hypertension and visual failure. MRI of the brain and optic nerve revealed enhancement and swelling of the optic nerve sheaths and optic discs. MRV findings were compatible with chronic veno-occlusive disease. Bone marrow aspiration and biopsy demonstrated an increase of aggregates of intermediate and mature plasma cells. The CSF pressure was markedly elevated. His clinical condition continued to deteriorate and he expired 3 years and 5 months from the onset of his illness. Although, overproduction of vascular endothelial growth factor has been reported and is being considered to be the possible cause of vascular hyperpermeability, the chronic venous sinus thrombosis may play an important role in the pathogenesis of intracranial hypertension and visual failure.

Clinical response to thymectomy in patients with myasthenia gravis varies in terms of timing and degree of improvement. Electrophysiological test is a reasonably reliable and objective way to evaluate neuromuscular transmission in these patients. The purpose of this study was to evaluate the electrophysiological response before and after thymectomy by repetitive nerve stimulation test in order to estimate the timing of initial improvement, progress and degree of improvement after thymectomy. According to electrophysiological findings, it appeared that neuromuscular transmission in these patients might have begun to improve even as early as one week after thymectomy and steadily improved by the end of one year of the study corresponding to clinical improvement.

There has been controversy whether oculopharyngodistal myopathy (OPDM) commonly seen in Japan is a distinct disease entity or a variant of oculopharyngeal muscular dystrophy (OPMD) initially described in French-Canadians and has since been reported in other ethnic groups. Both diseases have autosomal dominant inheritance and OPDM patients are clinically similar to OPMD with slowly progressive ptosis, ophthalmoplegia and dysphagia except that most of the former usually have distal as opposed to proximal weakness and most of them are genetically different from the latter The authors report here 2 siblings with clinical features of OPDM. This entity is rare outside Japan and this is the first family to be reported from Thailand

Differentiation of dementia with Lewy bodies (DLB), vascular dementia (VAD), and Alzheimer's disease (AD) is difficult in clinical practice. Several new techniques have been used for differentiation of various types of dementia. Among these techniques 123I-meta-iodobenzylguanidine (MIBG) uptake was reported to have benefit in distinguishing DLB from AD. The authors study the role of MIBG as a tool for differentiation of DLB, AD and VAD.Patients with dementia were recruited to the study by DSMIIIR criteria. Diagnosis of each dementia type was made by standard clinical criteria. Brain imagings and 131I-MIBG uptake were performed in all the studied patients.Five DLB, 3 AD and 3 VAD patients were clinically diagnosed. The heart/mediastinum (H/M) ratio in 4 out of 5 in DLB was significantly lower than H/M ratio in patients with AD and VAD. AD patients had the highest uptake of MIBG MIBG uptake of VAD patients was in the range between AD and DLB but the values were close to the AD group.131I-MIBG is helpful in differentiating DLB from AD.

Thymectomy has gained widespread acceptance as a treatment for patients with myasthenia gravis (MG). Patients with myasthenia gravis who had undergone thymectomy by extended transsternal approach between 1981 and 1987 were retrospectively reviewed to evaluate the result of thymectomy, time to remission, time to maximum improvement and factors influencing remission after thymectomy. There were 128 patients, 45 men and 83 women and the mean ages at the time of thymectomy were 35.7 and 32.2 years respectively. After thymectomy, 41.2% of the patients were in remission, 53% improved and 5.8% had no response. The remission rates at 1, 2, 5 and 10 years after thymectomy were 9%, 17%, 37% and 53% respectively and the median time to remission was 9 years. The maximum improvement rates at 1, 2, 5 and 10 years after thymectomy were estimated to be 30%, 40%, 57% and 78% respectively and the median time to maximum improvement was 3.6 years. Patients with ocular MG, longer duration of symptoms before thymectomy and atrophic thymus gland appeared to take longer to achieve remission although none of the factors was significantly associated with the time to remission. Thymectomy is beneficialfor MG patients with satisfactory remission and improvement rates. It is recommended that thymectomy should be advocatedfor these patients early in the course of the disease because the duration of the symptoms appeared to be the main determinant of the outcome.

Hiccups is a rare and unfamiliar presenting symptom of multiple sclerosis. Patients admitted to Ramathibodi Hospital from 1969 to 1992 who had a clinical diagnosis of multiple sclerosis were reviewed The presenting symptoms and neurological signs were analysed. The clinical features and course of the disease of cases who initially presented with intractable hiccups were studied in detail. There were 4 cases out of a total of 47 cases (8.5%) who presented with hiccups. These patients all had relapse and remission and two of them had a rather fulminant course of illness. Therefore, multiple sclerosis should be seriously considered as a possible cause of intractable hiccups. It may be of benign or malignant form. In the latter, the patients may develop quadriparesis within hours or days and respiratory failure may ensue. They usually respond well to high dose intravenous corticosteroids especially pulse methylprednisolone.

The clinical features and outcome of the treatment of aspergillosis of the central nervous system (CNS) in Thai patients are presented. The patients who were diagnosed as having CNS aspergillosis by tissue biopsy or culture from January 1, 1991 to December 31, 2000 were retrospectively reviewed. The study variables including age, sex, underlying disease, symptoms and signs, neuro-imaging studies, pathological findings and outcome of treatment, are described. There were seven cases of aspergillosis of the central nervous system. Four patients were male. The median age was 65 years (range 36-78 years). The most common underlying disease was diabetes mellitus (4/7; 57.1%). Two patients (28.6%) had no underlying disease. The most common primary site of infection was the paranasal sinuses (6/7; 85.7%). The most common clinical presentation was headache (6/7; 85.7%). Common neurological signs included multiple cranial nerve palsies (5/7; 71.4%) and alteration of consciousness (3/7; 42.9%). The median duration of the symptoms prior to admission was 60 days (range 8-180 days). All patients were treated with intravenous antifungal agents at high doses. Extensive surgery was performed in 6 patients. The mortality rate was very high (6/7; 85.7%). The median time from diagnosis and treatment to death was 53 days (22-720 days). Aspergillosis of the CNS should be considered in those with clinical features of headache, multiple cranial nerve palsies and alteration of consciousness accompanied by sinusitis, especially in elderly and diabetic patients. It remains a catastrophic opportunistic infection in spite of the current intensive and aggressive treatment.

Eight cases of Streptococcus suis (S. suis) infection between 1993-1999 were retrospectively studied. There were 6 cases of meningitis and 2 cases of endocarditis. Acute meningitis with early sensorineural hearing loss was the characteristic feature and the most common presentation of S. suis infection. S. suis endocarditis is a rare presentation in Thailand. This organism was often mistaken for Streptococcus pneumoniae or Streptococcus viridans. In this study, this was true in five cases in whom S. suis was identified later. However, the rapid diagnosis of S. suis meningitis may rely on Gram stain of the CSF in the setting of acute meningitis with hearing loss. These cases were treated with intravenous penicillin or ampicillin with a mean duration of 4 weeks. This treatment was very effective and there was no relapse among these patients.

The concentrations of penicillin in the cerebrospinal fluid (CSF) were compared simultaneously with those in the serum in 17 patients with syphilis. The antibiotic concentrations were measured by the agar well diffusion method. There were no detectable concentrations of penicillin in the CSF after administration of benzathine penicillin 2.4 megaunits, benzathine penicillin 7.2 megaunits, procaine penicillin in aluminium monostearate (PAM) 12 megaunits, or aqueous procaine penicillin G 2.4 megaunits. Only after high doses of aqueous penicillin G 24 megaunits daily or aqueous penicillin G 2 megaunits daily together with oral probenecid 2 g daily was penicillin detectable in the CSF. The concentrations after the latter regimen were the highest and much higher than the minimum inhibitory concentration for Treponema pallidum.