Case report Acute bilateral thalamic necrosis in a child with Mycoplasma pneumoniae CS Ashtekar DCH MRCPCH, Clinical Fellow, Paediatric Intensive Care; T Jaspan FRCP FRCR, Consultant, Department of Radiology; D Thomas FRCPCH, Consultant, Department of Child Health; V Weston MRCP MRCPath Consultant, Department of Microbiology and Public Health; NA Gayatri MD MRCP MRCPCH, Registrar in Paediatric Neurology; WP Whitehouse* FRCP FRCPCH, Consultant, Department of Paediatric Neurology, Queen’s Medical Centre, Nottingham, UK. *Correspondence to last author at Academic Division of Child Health, E Floor East Block, Queen’s Medical Centre, Nottingham NG7 2UH, UK. E-mail: william.whitehouse@nottingham.ac.uk A previously neurodevelopmentally intact 5-year-old male was admitted to hospital with a right lower lobe pneumonia with pleural effusion, subsequently confirmed to be a Mycoplasma pneumoniae infection. On the seventh day of the illness he had a prolonged generalized tonic or tonic–clonic convulsion, requiring intubation and ventilation. He was slow to regain consciousness (Child’s Glasgow Coma Score 7–10 over 6 days) and brain imaging with CT and then MRI demonstrated bilateral thalamic lesions with oedema and central haemorrhage suggestive of acute bilateral thalamic necrosis, without striatal or white-matter involvement. He was treated with a 2-week course of erythromycin, and as an autoimmune process was considered possible, 5 days of intravenous methylprednisolone (20mg/kg/day) followed by a 4-week oral prednisolone taper. He made a slow recovery over the next few weeks with almost complete neurological recovery by 2 months but with significant dysarthria, drooling, and a mild left hemiparesis. At 9 months, significant dystonia continued to affect his speech and, together with tremor, his upper-limb fine motor function bilaterally. His gait, personality, and higher cognitive functions appeared to have recovered fully. Although acute striatal necrosis, acute disseminated encephalomyelitis, and encephalitis have been reported with Mycoplasma pneumoniae and a similar picture of acute bilateral thalamic necrosis with influenza-A (‘acute necrotizing encephalopathy’), this is the first reported case of Mycoplasma pneumoniae-associated isolated acute bilateral thalamic necrosis. 634 Mycoplasma pneumoniae (M. pneumoniae) is a common cause of atypical pneumonia, endemic to most areas of the world with epidemics at 4 to 7 year intervals, when infection rates may reach 35% in children (Foy et al. 1979). Neurological complications may occur in 2 to 5% of patients (Fernandez et al. 1993) and include encephalitis, meningitis, cranial and peripheral neuropathies, and acute disseminated encephalomyelitis. Three pathophysiological mechanisms have been postulated: direct invasion, an autoimmune process, and a neurotoxic effect (Fernandez et al. 1993). Acute bilateral necrosis of the corpus striatum (consisting of the caudate and lentiform nuclei) has been associated with several neurological disorders (Leuzzi et al. 1998). We report a child with acquired neurological dysfunction associated with acute bilateral haemorrhagic necrosis of the thalami with M. pneumoniae pneumonia with pleural effusion. Case report A neurodevelopmentally intact, healthy 5-year-old male was admitted with a 5-day history of lethargy, weakness, dizziness, fever, and coughing. He was on oral penicillin. On admission to his local district general hospital he was mildly tachypnoeic. A chest radiograph revealed right lower lobe consolidation with pleural effusion. His white cell count was 9.39 × 109/l with neutrophilia. Intravenous benzylpenicillin and ceftriaxone were given. Thirty hours after admission he had a prolonged generalized tonic or tonic–clonic convulsion, received rectal diazepam, Developmental Medicine & Child Neurology 2003, 45: 634–637 Downloaded from https:/www.cambridge.org/core. Columbia University Libraries, on 16 Jun 2017 at 05:07:17, subject to the Cambridge Core terms of use, available at https:/www.cambridge.org/core/terms. https://doi.org/10.1017/S0012162203001154 intravenous lorazepam, rectal paraldehyde, and required intubation and ventilation. This was associated with hyponatraemia (sodium 124mmol/L). Paired urine and plasma electrolytes and osmolalites were consistent with inappropriate secretion of antidiuretic hormone. Unenhanced head CT demonstrated bilateral low-density thalamic lesions (Fig. 1). At thoracocentesis, 395mL of straw-coloured pleural fluid was aspirated, containing 51g/L of protein, no cells, and no organisms (including acid fast bacilli). All cultures were negative. Oral erythromycin was added following pleural fluid aspiration. He was transferred to the regional paediatric intensive care unit, at the Queen’s Medical Centre, Nottingham, in view of his continued unconsciousness and lack of respiratory effort, after 30 hours off sedation. On admission he had a modified Child’s Glasgow Coma Score of 7 (Tatman et al. 1997). The pupils were equal, reactive to light, and the fundi normal. Reflexes were brisk with bilateral extensor plantars and ankle clonus and, at best, he was localizing to pain. He had a diffuse erythematous blanching rash predominantly over the upper trunk and upper limbs. The cardiovascular system was stable without inotropic support. A lumbar puncture was not performed in view of the prolonged nature of the convulsions, low Child’s Glasgow Coma Score, and the CT appearance. MRI showed bilateral thalamic lesions with oedema and central haemorrhage suggestive of acute bilateral thalamic necrosis (Fig. 2a, b). Following intravenous contrast, faint enhancement was identified around R L Figure 1: Axial unenhanced CT demonstrating symmetrical hypodense swelling of the thalami. Third ventricle is effaced and lateral ventricles mildly dilated. the periphery of the haemorrhagic areas (Fig. 2c). Magnetic resonance venography was normal. The EEG demonstrated slow-wave activity, sometimes more marked on the right, with no epileptic discharges. Serum complement fixation test was positive for M. pneumoniae at a titre of 512 with a confirmatory M. pneumonia IgM of ≥ 32 and IgG of 32 tested by immunofluorescence antibody testing (Atypical Pneumonia Unit, PHLS, Central Public Health Laboratory). Consequently erythromycin was continued for a total of 2 weeks and all other antibiotics were stopped. On repeat thoracocentesis the pleural fluid had protein 29g/L, lactate 1.82mmol/L, glucose 5.7 mmol/L, no organisms (including acid fast bacilli), and all cultures (bacterial and viral) were negative. Other investigations were either normal or negative: erythrocyte sedimentation rate, clotting profile, thrombophilia screen, electrolytes including calcium, phosphate and magnesium, liver function tests, lactate, ammonia, very long chain fatty acids, carnitine levels, antinuclear cytoplasmic antibodies, antiphospholipid and antilupus antibodies, dsDNA antibody, thyroid function test, thyroid peroxidase antibodies, immunoglobulin levels, compliment factors (C3, C4), autoimmune screen, serology for measles, mumps, herpes simplex and cytomegalovirus, urine organic and aminoacids, and stool virology. Intravenous methylprednisolone, at a dose of 20mg/kg/day once a day, was commenced. Over the next 5 days he remained neurologically stable with a Child’s Glasgow Coma Score between 8 and 10. There was occasional eye opening to painful stimuli, and pupils were equal and reacting. Doll’s eye movements were complete, and there was marked hypertonia in all limbs, which settled with oral baclofen. On the paediatric intensive care unit he had recurrent brief tonic or tonic–clonic seizures or spasms, and was extubated after a week. Over the next 3 weeks he made slow but steady improvement neurologically, and a repeat CT of the head then showed resolving low attenuation abnormality in the thalami (Fig. 3). A complement fixation test for Mycoplasma pneumoniae was positive at a lower titre of 128, 4 weeks after the onset of respiratory symptoms with an Mycoplasma pneumonia IgM titre of ≥ 32 and IgG ≥ 64 by immunofluorescence antibody testing. Visual evoked potentials, evoked retinography, and auditory brain-stem evoked responses were normal. Methylprednisolone was changed to oral prednisolone after 5 days, then tapered over 4 weeks. He remained on a reducing dose of phenytoin for 4 weeks. At 4 weeks from the onset of illness, he was making eye contact with his parents, smiling, and vocalizing in response to voice. He was generally hypotonic with brisk tendon reflexes and bilateral extensor plantar responses, and had spontaneous voluntary movements in all his limbs. There was relative weakness or neglect of the left side of the body. Eight weeks from onset he was off steroids and phenytoin, was cheerful, talking, walking, and running, although he was a little dysarthric and had a mild left hemiparesis. Nine months later he continued to have significant dystonia affecting his speech and upper-limb fine motor function and action tremor, bilaterally. The MRI was much improved. His parents felt there had been no major change in personality, comprehension, or cognitive ability. Case Report Downloaded from https:/www.cambridge.org/core. Columbia University Libraries, on 16 Jun 2017 at 05:07:17, subject to the Cambridge Core terms of use, available at https:/www.cambridge.org/core/terms. https://doi.org/10.1017/S0012162203001154 635 His parents have given written consent for us to publish this case report. Discussion We report the case of a 5-year-old male who had acute bilateral thalamic necrosis with evidence of an acute Mycoplasma pneumoniae pneumonia, a complement fixation titre of 512, 7 days after the onset of respiratory symptoms and a subsequent four-fold drop to a titre of 128, 4 weeks later. Further confirmatory serology was obtained with high levels of IgM in the two samples and a rising level of IgG by immunofluorescence antibody testing. Acute bilateral striatal necrosis with Mycoplasma pneumoniae has been reported in the literature (Saitoh et al. 1993, Brandel et al. 1996, Larsen and Crisp 1996, Sakoulas and George 2001). Striatal encephalitis and necrosis can manifest clinically with encephalopathy and extrapyramidal symptoms including rigidity (Sakoulas and George 2001). Various mechanisms including direct invasion of brain tissue by the organism, production of a neurotoxin or an autoimmune phenomenon induced by the immune system response to the organism, analogous to acute disseminated encephalomyelitis, have been implicated in the pathogenesis of CNS disease associated with Mycoplasma pneumoniae (Fernandez et al. 1993). The time course seen in some of the cases is consistent with an autoimmune process, as in our patient, with acute encephalopathy developing 1 week after the onset of the respiratory illness. MRI and CT of the head in this case demonstrated bilateral thalamic necrosis with normal appearances of the striatal structures and white matter. Thalamic infarction due to arterial or venous causes was considered but excluded by imaging, which subsequently b a R L c R L Figure 2: (a) Axial T2-weighted image. There is heterogeneous hyperintense abnormality centred upon thalami, extending into adjacent posterior capsular regions, sparing striatal structures. (b) Coronal T1-weighted image showing central hyperintensity, reflecting haemorrhage, within the hypointense thalami. Note swelling with compression of third ventricle. (c) Axial T1-weighted image following intravenous administration of Gadolinium DTPA. Faint enhancement is present around periphery of central areas of haemorrhage. 636 R Developmental Medicine & Child Neurology 2003, 45: 634–637 Downloaded from https:/www.cambridge.org/core. Columbia University Libraries, on 16 Jun 2017 at 05:07:17, subject to the Cambridge Core terms of use, available at https:/www.cambridge.org/core/terms. https://doi.org/10.1017/S0012162203001154 L demonstrated considerable resolution of the lesions, paralleled by the almost complete early neurological recovery. Other possible causes of thalamic necrosis include congenital heart disease, migraine (Garg and DeMyer 1995), infectious vasculitis (aseptic meningoencephalitis), and recently, influenza A-associated acute necrotizing encephalopathy (Voudris et al. 2001), which featured pontine inflammation in addition to identical acute haemorrhagic bilateral thalamic necrosis. This is, to our knowledge, the first reported case of M. pneumoniaeassociated isolated acute bilateral thalamic necrosis. DOI: 10.1017/S0012162203001154 Accepted for publication 29th April 2003. Acknowledgements We would like to thank Dr TG Harrison, Head of the Atypical Pneumonia Unit PHLS Central Public Laboratory for the Mycoplasma reference serology by immunofluorescence. R L Figure 3: Axial unenhanced CT scan. There is residual central thalamic hypodensity with faint surrounding mild hyperdensity, possibly representing blood products or calcification. Third ventricle is revisualized and lateral ventricles are smaller with some widening of cerebral sulci. References Brandel JP, Vidailhet M, Noseda G, Harpey JP, Agid Y. (1996) Mycoplasma pneumoniae post infectious encephalomyelitis with bilateral striatal necrosis. Mov Disord 11: 333–336. Fernandez CV, Bortolussi R, Gordon K, Lee SHS, Gatien JG, Shahdrabadi MS. (1993) Mycoplasma pneumoniae infection associated with central nervous system complications. J Child Neurol 8: 27–31. Foy HM, Kenny GE, Cooney MK, Allan ID. (1979) Long-term epidemiology of infections with Mycoplasma pneumoniae. J Infect Dis 139: 681–687. 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(2001) Brain MRI findings in influenza A-associated acute necrotizing encephalopathy of childhood. Eur J Paediatr Neurol 5: 199–202. Case Report Downloaded from https:/www.cambridge.org/core. Columbia University Libraries, on 16 Jun 2017 at 05:07:17, subject to the Cambridge Core terms of use, available at https:/www.cambridge.org/core/terms. https://doi.org/10.1017/S0012162203001154 637