A 35-year-old Caucasian woman with Cyclin-Dependent Kinase-like 5 gene (CDKL5) deficiency disorder presented with recurrent admissions via the emergency department for productive cough and low-grade fever.
She is, to the our best knowledge, the oldest surviving patient with CDKL5 deficiency. Each time she was diagnosed with aspiration pneumonia.
She was admitted to the hospital for the sixth time in six months. Her case was discussed in multi-disciplinary meeting and it was decided to get a neurology, and gastroenterology review to assist in reducing recurrence of aspiration pneumonia.
As part of overall assessment, it was suggested to get a cardiology review after radiology reported a presumed cardiac pacemaker on her chest x-ray. During the gastroenterology ward round, it was concluded that the patient has a vagal nerve stimulator (VNS), and not a cardiac pacemaker. In consultation with neurology, she was prescribed midazolam once a day, via per-cutaneous endoscopic gastrostomy tube (PEG). These measures improved her symptoms, and she was discharged back to the nursing home.
A 35-year old Caucasian woman previously diagnosed with CDKL5 deficiency was admitted for the sixth consecutive time in six months, for productive cough with low grade fever. She was previously been tried on several anti-epileptics. She is currently on perampanel 4 and 6mg via PEG alternate daily.
She also had severe learning difficulties and scoliosis. Her Rockwood Clinical Frailty Score was 7. Her nutrition was managed by PEG-feed. She was bed-bound and used a wheelchair with transfer from and to the bed via a hoist.
On admission her temperature was 37.4 celsius, heart rate 82 /minute, blood pressure 118/70mmHg, respiratory rate 20/min, oxygen saturation 96% on air. Blood tests revealed CRP 18 (0-5), white cell count 9.15 (4-11 x 109/l), neutrophils 4.1 (2-7.5x 109/l). Blood cultures were negative. She was empirically managed with amoxicillin and metronidazole intravenously. Her chest radiograph showed some patchy changes suggesting aspiration pneumonia.
Her case was discussed with gastroenterology, neurology and the speech and language therapy teams. Her aspiration pneumonia was found to be multifactorial; due to seizures and increased oro-pharyngeal secretions. Following normal X-ray tubogram, PEG tube was excluded as possible cause. Her PEG feeding was optimised to daily total 1200-1240 kilo calories
As part of overall assessment prior to discharge it was suggested to get a cardiology review for presumed cardiac pacemaker as reported by radiology on the chest x-ray. During the gastroenterology ward round, it was concluded that the patient has a left sub-clavicular vagal nerve stimulator implanted and not a cardiac pacemaker. In consultation with neurology, her seizure frequency improved with optimisation to 7.5 mg once a day midazolam (12.5mg/5 ml) syrup via PEG. She was discharged back to the nursing home.
Figure 1; Plain Chest X-ray; Antero-Posterior view, with Vagal Nerve Stimulator Generator (VNS). Bilateral elevated diaphragm with some patchy shadows on left lung base.
Differentials of sub-cutaneous devices
Varying in location of placement, and serving varied functions, the sub-cutaneous placed devices include;
- Cardiac pacemaker, PPM and ICDs
- Intrathecal drug delivery system (IDDS) – morphine pump
- Vagal nerve stimulator device (VNS) – as in our patient.
What is CDKL5 disorder?
CDKL5 stands for cyclin-dependent kinase-like 5 deficiency disorder. The gene is located on the X chromosome. Previously thought to be part of Rett Syndrome spectrum back in 1985,1 it is now seen as a separate entity with varying severity.2
Although a great majority is inherited, there are cases with single occurrence in a family from a de novo mutation. Suggested incidence is believed to be approximately one in 40,000 -60,000 live births, making it one of the most common forms of genetic epilepsy.3
Life expectancy is unknown due to underdiagnosis in childhood and adolescence. Prognosis is commonly poor with severe psychomotor deficits and intractable seizures remaining into adulthood.
The clinical management challenges are multi-factorial and almost always need multi-disciplinary team approach towards managing the complex needs. The biggest challenge is the seizures that change as patients age.4
Studies have found vagal nerve stimulators to be a safe and effective adjunct to management of CDKL5 deficiency associated epilepsy. However, they recommended further work to determine optimal setting and therapeutic potential.5
- Awareness of genetic disorders that require management with multi-disciplinary approach.
- Sub-clavicular device is not always a cardiac pacemaker or implantable cardiac defibrillator. It may be a vagal nerve stimulator (VNS).
- Understanding of the device prevents unnecessary utilisation of NHS resources.
Dr Mansoor Zafar, Gastroenterology Specialty Registrar, General Internal Medicine
Dr Tila Muhammad, Locum Consultant Gastroenterology
Dr Apurva Lunia, SHO, General Internal Medicine
Dr Muhammad Toqeer, Consultant Gastroenterology
Dr Mark Whitehead, Consultant Physician, Gastroenterologist, Director of Medical Education.
Conquest Hospital, East Sussex Healthcare NHS Trust
- Hanefeld F. The clinical pattern of the Rett syndrome. Brain Dev. 1985;7(3):320-5.
- Kalscheuer VM, Tao J, Donnelly A, Hollway G, Schwinger E, Kübart S, et al. Disruption of the serine/threonine kinase 9 gene causes severe X-linked infantile spasms and mental retardation. Am J Hum Genet. 2003;72(6):1401-11.
- Weaving LS, Christodoulou J, Williamson SL, Friend KL, McKenzie OL, Archer H, et al. Mutations of CDKL5 cause a severe neurodevelopmental disorder with infantile spasms and mental retardation. Am J Hum Genet. 2004;75(6):1079-93.
- Moseley BD, Dhamija R, Wirrell EC, Nickels KC. Historic, clinical, and prognostic features of epileptic encephalopathies caused by CDKL5 mutations. Pediatr Neurol. 2012;46(2):101-5.
- Lim Z, Wong K, Downs J, Bebbington K, Demarest S, Leonard H. Vagus nerve stimulation for the treatment of refractory epilepsy in the CDKL5 Deficiency Disorder. Epilepsy Res. 2018;146:36-40.
*Consent was obtained from the patient's mother.