Archives

  • 2018-07
  • 2019-04
  • 2019-05
  • 2019-06
  • 2019-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • 2019-12
  • 2020-01
  • 2020-02
  • 2020-03
  • 2020-04
  • 2020-05
  • 2020-06
  • 2020-07
  • 2020-08
  • 2020-09
  • 2020-10
  • 2020-11
  • 2020-12
  • 2021-01
  • 2021-02
  • 2021-03
  • 2021-04
  • 2021-05
  • 2021-06
  • 2021-07
  • 2021-08
  • 2021-09
  • 2021-10
  • 2021-11
  • 2021-12
  • 2022-01
  • 2022-02
  • 2022-03
  • 2022-04
  • 2022-05
  • 2022-06
  • 2022-07
  • 2022-08
  • 2022-09
  • 2022-10
  • 2022-11
  • 2022-12
  • 2023-01
  • 2023-02
  • 2023-03
  • 2023-04
  • 2023-05
  • 2023-06
  • 2023-08
  • 2023-09
  • 2023-10
  • 2023-11
  • 2023-12
  • 2024-01
  • 2024-02
  • 2024-03
  • Also considered very rare is progressive

    2022-06-17

    Also considered very rare is progressive encephalomyelitis with rigidity and myoclonus (PERM); sometimes called Stiff Person Syndrome Plus (SPS Plus) and with antibodies to glutamic BMS-754807 mg decarboxylase (GAD). However, PERM is now increasingly found with glycine receptor antibodies (GlyR-Ab), in adults4, 5 and has been described in children.6, 7 The phenotypes associated with GlyR-Abs are beginning to widen as more patients are identified.8, 9
    Case report A previously-well 3 year 5 month old Chinese boy experienced increased moodiness and agitation for 4–5 days, urinary incontinence in sleep and two focal seizures starting with left upper limb twitching; one with blank unresponsive staring for 15 min and a second with slurred speech and nodding of head to questions, lasting 45 min and aborted with benzodiazepines in hospital. There was no fever, coryzal symptoms, vomiting, diarrhoea, headaches, dysuria or preceding head injury, trauma, recent travel or infective contacts. Development was age-appropriate with no past or family history of seizures, epilepsy or developmental delay. He was well hydrated and afebrile with no neurocutaneous stigmata and normal systemic examination apart from a papular rash over the left temporal region and atopic eczema. Initial investigations including electroencephalogram (EEG) were normal (Table 1). The patient was incidentally noted to have nasopharyngeal aspirate briefly positive on immunofluorescence for Parainfluenza 3, and Beta thalassaemia minor. No further seizures occurred but paroxysmal behavioural outbursts persisted lasting 5–35 min, with screaming, sudden awakening from sleep, non-specific pain, agitation, obsessive hand-cleaning and picking up non-existent rubbish. He received intravenous levetiracetam followed by oral lorazepam due to concerns that levetiracetam might exacerbate his behaviour. He was discharged well after 4 days but was readmitted on day 25 of illness with three new focal left upper limb seizures: two 2–3 min tonic seizures and one 10-min tonic-clonic seizure. Post-ictal sleepiness and left upper limb weakness and clumsiness were noted. There was no inter-current illness, fever, vomiting, headaches, photophobia, loss of appetite or loss of weight. Cranial nerve examination was normal but his left lower limb lagged behind when running and a mild left facial weakness was seen on smiling, consistent with Todd's paresis. This rapidly resolved. Further investigations were normal (Table 1). He was restarted on oral levetiracetam 100 mg BD and returned home well. The following are the Supplementary video related to this article: Serum GlyR-Ab was positive (at 1:160; normal value <1:20) and anti-NMDAR, anti-VGKC and Dopamine 2 Receptor (D2R) antibodies were negative. He returned to normal by day 88 and benzhexol was weaned off. Clinical improvement correlated well with a gradual reduction in glycine receptor antibody titres, which dropped to 1:40 by day 180 of illness (Fig. 1) and 1:20 at 23 months follow-up. At his last clinic review 31 months after initial presentation, there were no recurrence of symptoms.
    Discussion We report a novel phenotype for glycine receptor antibody-mediated neurological disease in children. The spectrum of phenotypes seen with this and other anti-neuronal antibodies is increasing, with NMDAR now associated with movement disorders without encephalopathy. Glycine receptor antibodies were initially reported with the clinical phenotype of progressive encephalomyelitis with rigidity, myoclonus and hyperekplexia.3, 5 Carvajal et al. reported an extended spectrum of clinical phenotype, with 33 patients with progressive encephalomyelitis with rigidity and myoclonus, two with Stiff Person Syndrome; five with limbic encephalitis or epileptic encephalopathy, two with mainly brainstem features, two with demyelinating optic neuropathies and one with an unclear diagnosis. Our patient's clinical phenotype is more typical of VGKC-associated limbic encephalitis or NMDAR encephalitis. However this patient was negative for VGKC-complex, NMDAR antibodies and D2R antibodies. FBDS was considered in the differential diagnosis but the movements were heterogenous, pervasive and continuous – in contrast to the stereotyped and paroxysmal movements seen in FBDS. No ictal EEG changes were observed during the movements, though ictal EEG patterns are only present in 24% of FBDS.