Case Study - An unusual cause for a confused state

This patient's rapid deterioration in his mental state made Dr Louise Newson seek an urgent specialist opinion.

Mr R, a 74-year-old man, presented at the surgery with his wife. She had noticed that over the past month he had become more confused.

His short-term memory was affected, and she said he kept repeating himself. He was also quite forgetful and had left taps running in the house.

He was generally well and independent. His past history of note was rheumatoid arthritis (RA) and hypertension. He had been taking methotrexate for his RA but this had been discontinued due to leucopenia.

As an alternative, he had recently received his fifth dose of adalimumab, the antitumour necrosis factor (anti-TNF) treatment, which had made a dramatic improvement to his joints. His BP was well controlled with amlodipine and lisinopril. He was also taking aspirin and simvastatin.

General examination was unremarkable and he scored 5/10 in the Abbreviated Mental Test (AMT). The working diagnosis was dementia and he was referred to the local memory clinic.

He came to see me two weeks later, again with his wife. She was increasingly concerned.

He had been very sleepy and had also been complaining of a headache. He was struggling with simple tasks, for example he could not even remember how to put on his jumper.

He was also doing very odd things - he had been using his pliers to stir his coffee.

Neurological examination revealed an extensor plantar response on the right with slightly brisker reflexes in his right leg. Power was difficult to assess as the patient was finding it difficult to comply with simple commands. His AMT score was now 1/10.

As there had been a marked deterioration in his condition, I admitted him to our local hospital for further investigations.

Surprise diagnosis
I was very surprised, 10 days later, to receive his discharge summary from the hospital stating his diagnosis was TB meningitis (TBM).

He had had TB when he lived in Ireland 45 years ago and it was thought that the TB was reactivated after the adalimumab treatment for his RA.

TBM makes up a small proportion of clinical TB but is important because of its high mortality and chronic morbidity.

TBM typically starts with vague headache, lassitude and fever. Focal neurological signs may then develop over the following weeks. Cognition may be impaired and seizures can also be common.

A lumbar puncture is used with the clinical history and examination to come to a diagnosis. Patients with TBM often have a lower blood neutrophil count. Examination of their CSF typically reveals a lower neutrophil count (as indeed was the case for this patient), lower glucose and higher protein levels than are seen in patients with bacterial meningitis.1

Discussion
The product information clearly states that patients should be evaluated for TB before treatment with adalimumab. Patients who have previously received adequate treatment for TB can start adalimumab but should be monitored every three months for possible recurrence.

In addition, patients should be advised to seek medical attention if symptoms suggestive of TB (persistent cough, weight loss and fever) develop. The British Thoracic Society has produced guidelines on this.2

Outcome
Mr R has been receiving anti-TB medication and has tolerated the side-effects admirably. His mental state has improved to normal according to his wife and he has no physical sequelae from the infection.

Dr Newson is a GP in the West Midlands

References

1. Thwaites G E, Chau T T, Stepniewska K, et al. Diagnosis of adult tuberculous meningitis by use of clinical and laboratory features. Lancet 2002; 360(9342): 1,287-92.

2. British Thoracic Society Standards of Care Committee. BTS recommendations for assessing risk and for managing Mycobacterium tuberculosis infection and disease in patients due to start anti-TNF-a treatment. Thorax 2005; 60: 800-805.

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