Hyperkalemic Periodic Paralysis
F Brancati1, F. et al. (2003) Severe infantile hyperkalaemic periodic paralysis and paramyotonia congenita:
broadening the clinical spectrum associated with the T704M mutation in SCN4A Journal of Neurology
Neurosurgery and Psychiatry 2003;74:1339-1341
The VV family is a three generation kindred with nine members affected by a remarkably severe,
homogeneous hyperPP/PMC phenotype. The onset of paralytic episodes was around six to nine
months of age in all patients. During infancy and childhood, the episodes were frequent (up to
two to three a week), lasting 10 minutes to two hours and were usually accompanied by muscle
stiffness, mainly at the lower limbs. Nocturnal, potentially life threatening episodes of complete
paralysis with respiratory difficulties were experienced in the first years of life. During
adolescence, episodes were always related to a precipitating factor (that is, rest after exercise,
exposure to cold, alcohol intake, fasting), and carbohydrate intake sometimes alleviated the
paralysis. The frequency and severity of episodes insidiously worsened over the years. In
adulthood, the attacks occurred with daily frequency and arose spontaneously or with minimal
provocation (for example, sitting down for a short time to have lunch or a short drive), becoming
very debilitating and interfering with most daily activities. The main episodes lasted up to several
hours, but focal weakness in a muscle or group of muscles (for example, "floppy foot") could
persist for days. Diffuse inter-episode weakness, mainly in the proximal muscles, invariably
developed around the fourth to fifth decade and was slowly progressive, with difficulty in climbing
stairs and carrying shopping. Since the neonatal age, lid-lag phenomenon and profuse sweating
were typical prodromal signs of an episode. Acetazolamide (up to 1000 mg daily), chlorothiazide
(500 mg daily), and salbutamol (either orally 2 mg thrice daily or inhaled 200 µg nasally) were
completely ineffective in preventing or aborting the episodes of paralysis. Two patients (II:4 and
II:6) developed a cardiac arrhythmia in their 60s, and one of them (II:6) required a pacemaker
implantation
Malignant Hyperthermia
Rueffert, H., Olthoff, D., Deutrich, C. (2004) Malignant hyperthermia. Anesthesia 100:731-733
In the second family, a 15-year-old girl developed a tachycardia of 140 beats/min, 45 min after
induction of anesthesia. Carbon dioxide rose to 90 mmHg, followed by a metabolic acidosis (pH
7.21) and a maximal serum creatine kinase elevation of 1655 U/l. General anesthesia for an
operation on the spinal column was induced with thiopental, alfentanil, and vecuronium, and
was maintained with isoflurane. When MH was suspected to be the possible cause of the
symptoms, the isoflurane supply was interrupted and the symptoms rapidly declined. Dantrolene
was not administered. The susceptibility to MH was confirmed by the IVCT 3 months later, and
the histopathologic examination of a muscle biopsy also revealed the presence of central core
disease. A RYR1 Ile2453Thr (T7358->C) substitution was identified by DNA testing. The
patient’s mother, who also showed pathologic responses in the IVCT (MH-susceptible), carried
the same Ile2453Thr mutation, but both grandparents showed a diagnostic constellation similar
to that of family 1: both were found to be MH-negative in the IVCT, and neither carried the
familial mutation.
Myotonic Dystrophy
Nanayakkara et. al. (2003) A man with fever and a persistent handgrip Lancet 2003; 362: 1038
Over the course of 3 years, the febrile episodes increased in frequency, until they occurred
every 2 weeks. We re-evaluated all the previous results, and concluded that the patient was
unlikely to have either a chronic infection or malignancy. However, we noticed that there had
been slight increases in serum creatine-kinase (165-266U/L [normal<150]) during several
episodes. He had no complaints of muscular pain or weakness. In fact, he frequently rode
distances of 100 km on his racing bicycle. Finally, during one visit, we asked him to release his
fist after a firm handgrip and saw delayed relaxation of his flexed fingers. Then the typical facies
(figure), wasting of the sternocleidomastoids, and weakness of neck flexors became obvious,
providing sufficient evidence for a clinical diagnosis of myotonic dystrophy. DNA analysis
confirmed the diagnosis. The patient denied dysphagia, but we tested his swallowing, and found
oesophageal propulsion abnormalities and silent aspiration. Oesophageal pH-measurement
showed an increased acid reflux. 3 years after its appearance, the fever was explained by
repeated episodes of aspiration pneumonia. We prescribed physiotherapy, omeprazole, and an
antireflux diet, which rapidly reduced the episodes of fever. When last seen in May, 2003, he
had been free of fever for 2 years, and continued to do long-distance bicycle rides, even though
he had developed bilateral foot-drop, and was finding walking difficult.
Long QT Syndrome
Chuang, W-Y, et al. (2009) Fourteen-year follow-up in a teenager with congential long QT syndrome
masquerading as idiopathic generalized epilepsy. J. Am. Board Fam Med 22:331
A 17-year-old man was hospitalized for repeated convulsions. At home he had tonic-clonic
convulsions associated with upward gaze. These episodes usually lasted for 1 to 2 minutes. He
had full recovery shortly after the episodes without any significant neurological deficits. These
convulsions occurred approximately 4 to 5 times per year, beginning at age 12. The episodes
usually occurred at sleep and were often associated with urinary incontinence. He had been
diagnosed as having idiopathic epilepsy by a number of pediatric neurologists and was being
empirically treated with anticonvulants (carbamazepine, valproic acid, and phenytoin). During
physical examination he was alert and well developed. Electrolyte levels, including potassium,
magnesium, and calcium, were within normal range. Magnetic resonance imaging of the head
was normal. Neurologic findings, including hearing function, were also normal. An EEG was
obtained a day later and was normal when the patient was both awake and asleep. General
cardiac examination, echocardiogram, and coronary arteriography were unremarkable. There
was no history of seizures, syncope, or sudden death in any family members or close relatives.
The 12-lead ECG of his parents and sibling were unremarkable, showing QTc _420 ms for
each.
During his hospital stay, a generalized tonicclonic seizure during sleep with spontaneous
recovery was witnessed. A rhythm strip obtained immediately afterward showed sinus pause,
bifid T wave, and T wave alternans (Figure 1). A trademark dysrhythmia of unsustained torsade
de pointes (TdP) with a QTc duration of 518 ms (Figure 2) was recorded shortly after further
cardiac consultation was begun. A Holter recording obtained during another ictal episode
documented frequent runs of self-terminating polymorphic ventricular tachycardia and TdP
(Figure 3), ultimately leading to the final diagnosis. Genetic testing revealed a mutation of the
human ether-a-go-go-related gene (HERG or KCNH2) (a deletion of one base pair in exon 12,
2768delC) encoding the rapidly activating delayed rectifier cardiac potassium channel (IKr), a
finding consistent with LQT2 syndrome. Genetic analysisfor the patient’s family members and
other relatives was negative. LQT syndrome was diagnosed based on the “Schwartz and Moss”
clinical criteria,5 including the recording of a low heart rate for his age, T wave alternans,
notched T waves, prolonged QTc, and TdP. After informed discussion he decided against
having an implanted cardioverter defibrillator (ICD) because of a lack of financial support; thus a
pacemaker was implanted at that time. The antiepileptic drugs were discontinued and he was
started on a course of propranolol and spironolactone. After that, the patient was free of seizure
episodes until sudden cardiovascular collapse occurred 74 months later while he was eating a
meal. On arrival at the emergency department he was pulseless and apneic, and an ECG
showed ventricular fibrillation. Defibrillation was required twice before sinus rhythm and gasping
respiration returned. An ICD was placed and he was discharged 1 week later. He continued
taking propranolol and spironolactone. He returned to have his job as usual and was still
asymptomatic (without ICD shock) 38 months after the intervention.