Wernicke-Korsakoff Syndrome with Serum Positive Anti-NMDA-Receptor Antibodies – Case Files

THE CASE

A 60-year-old female of European background was admitted to a Neuropsychiatry Unit with a history of sub-acute onset of leg weakness, ataxia, confusion and poor self-care on a background of heavy periods of alcohol intake; drinking up to 4 L of cask wine per day.

Her presentation was characterized by disinhibition, disorientation, paranoid themes, confabulation and an extremely impoverished ability to learn and retain new information. Her language skills were intact.

Neurological examination yielded no ophthalmoplegia. However, dysdiadochokinesis, past pointing, and lower limb ataxia were present. There was no autonomic instability.

Further collateral history revealed multiple past presentations to the hospital with alcohol-related medical complications (pancreatitis, seizures) as well as episodes of acute confusion.

The clinical history and neuropsychological profile were in keeping with repeated episodes of subacute Wernicke’s Encephalopathy now culminating in a Korsakoff Syndrome. Read about Wernicke’s and Korsakoff’s Syndrome.

INVESTIGATIONS

Organic Screen revealed the following

• FBC, UEC, LFTs, TFTs, thyroid antibodies, copper, caeruloplasmin, Vitamin B12 (replaced by referring hospital), folate, Vitamin D, cANCA, pANCA normal
• Albumin 25 (L), protein 58 (L)
• Low serum iron and transferrin, normal ferritin
• Normal CRP
• ESR 35 (H)
• Weak positive ANA Nucleolar titre 40
• Serum NMDA receptor antibodies positive (including on repeat testing)
• HIV, Syphilis negative
• Ovarian tumour markers CA-125, CA19.9, CEA negative

MRI Brain showed diffuse atrophy with chronic white matter ischaemic changes (Figures 1 and 2). This is in keeping with long-term alcohol use and cerebrovascular disease.

Figure 1. MRI brain. T1-weighted sagittal section shows generalized atrophy, particularly in the superior aspect of the cerebellum (indicated by white arrow)

Figure 2: MRI brain. Axial FLAIR sequence. White arrows indicate widespread periventricular white matter changes.

SPECT showed no diagnostic features of a neurodegenerative process

CT abdomen and pelvis showed a cystic left adnexal lesion, likely ovarian

Pelvis USS demonstrated a simple left ovarian cyst measuring with a single non-vascular septation

EEG – Intermittent superimposed generalised slowing likely to be consistent with state, medication or acquired alcohol-related injury

HOW WAS THE PATIENT TREATED?

The patient was managed for behavioral disturbances with regular diazepam titrated up to 15 mg / day and olanzapine titrated up to 25 mg / day. Diversion techniques such as music therapy were also useful.

The case was discussed with the neurological team, who stated there were no clinical signs of Anti-NMDA-R ab encephalitis, however, CSF testing of Anti-NMDA-R abs would be more definitive. Given the patient’s mental state, she would have required a general anaesthetic to undergo lumbar puncture. The possibility of lumbar puncture and a trial of immunotherapy and consideration of surgical excision of the ovarian cyst if anti-NMDA-R abs were detected in the CSF was discussed with her guardian who declined further investigation.

The patient’s presentation remained stable, and she was transferred back to her local hospital. She was referred to the local gynaecology service for surveillance of the ovarian cyst.

SERUM ANTI-NMDA-R-ABS: POSSIBLE FALSE POSITIVE?

The false-positivity rate of serum Anti-NMDA-R abs is reported to be 0.4 – 3 % (Greta-Arribas, Titulaer, Torrents et al. 2014). False-positive rates decrease with the use of multiple detection techniques and CSF testing.

TAKE HOME MESSAGES

• Serum Anti-NMDA-R abs have been reported in neurodegenerative and psychiatric disorders other than that of Anti-NMDA-R ab encephalitis
• The specificity and sensitivity of Anti-NMDA-R abs are lower in serum than in CSF
• Pre-test probability is an important consideration when performing tests such as Anti-NMDA-R abs
• The corollary of this case is that if Anti-NMDA-R ab encephalitis is suspected and serum testing is negative, CSF should be tested as this has 100% sensitivity (serum sensitivity is 86%).

QUIZ