1. Clinical Studies of Hereditary Sensory and Autonomic Neuropathy Type 4

5th Asian and Oceanian Congress of Child Neurology, Istanbul Turkey, 1996, October

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Kenji Nihei,	Yutaka Awaya,	and Syouta Miyake.
1) Department of Pediatric Neurology, National Children's Hospital. 2) Department of Pediatrics, Seibo Hospital. 3) Yokohama Ryouiku-en, Tokyo, Japan.

Hereditary sensory and autonomic neuropathy (HSAN)is usually divided into six types(Liberfarb,1993).Type 4 of HSAN shows congenital insensitivity to pain with anhidrosis and autosomal recessive trait.

We studied 29 cases with HSAN type 4 in Japan and discussed the clinical signs. The male to female ratio was 18/11.Insensitivity to pain or heat, severe self injury, such as biting their own tongue or unexplained fever were noticed within the first six months of age in 15 of the 29 cases. Sensation of touch, itching and tickle were all intact. The average gestational week of the 29 cases was 38.5 weeks, the average birth weight was 2643g.Developmental milestones were delayed as follows: head control was at 4.1,months old (3-6), sitting alone was at 9.0 months old(7-15)and walking alone was at 17.8 months old(14-28)on average. Facial appearance was characteristic in about one-third of the cases. Head circumference was in the normal range, but in many cases it was under the average. About half of the cases showed muscle hypotonia with hyporeflexia. The average IQ was 73.5 in 3-to 4-year-olds, 46. 6 in 6-to 12-year-olds and 39.4 in children over 13 years old. Hyperkinetic mild mental delay was also characteristic. Because of mental delay and hyperkinesia, they could not learn the risk of pain and heat. There was a history of febrile convulsion in 17 of the 29 cases (58.6%). Epilepsy was seen in 5 of the 29. A high incidence of febrile convulsion or epilepsy and mental retardation suggests that HSAN type 4 not only involves the peripheral nerves, such as sensory and autonomic nerves, but also involves the central nervous system.

Serious complications were Charcot joints, repeated severe burns, osteomyclitis, bone fracture, traumas of tongue and mucous and hyperthermia or heat stroke due to anhidorosis. In some cases these complications were the cause of death. It is very important to prevent these complications. Further study is needed.

2. Seizures in Congenital Insensitivity to Pain with Anhidrosis (CIPA)

8th International Child Neurology Congress, Ljubljana, Slovenia,1998, September

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Yutaka Awaya,	Kenji Nihei,	Kikuko Ikeda.
1) Seibo International Catholic Hospital ,Dept. of Pediatrics ,Tokyo. 2) National Children’s Hospital ,Dept. of Pediatric Neurology ,Tokyo. 3) Chiba-Nishi Hospital ,Dept. of Pediatrics, Chiba. 4) Japan Association of Patients with CIPA (JA-CIPA) ; JAPAN.

CIPA is regarded as the same disease entity as hereditary sensory and autonomic neuropathy (HSAN) type 4 (Dyck) . The main clinical features include unexplained fever and repeated traumatic and thermal injuries due to lack of the first order afferent system. Not only peripheral but also CNS involvement is thought to occur in CIPA, e.g. mental retardation and hyperactivity.
We examined seizures as a manifestation of CNS involvement in CIPA. The genes responsible for CIPA were recently identified by Indo et.al. (1996).:The parents of 50 JA- CIPA patients consented to participate in this study.
Questionnaires regarding seizures were answered by all of the parents and some medical records were obtained from primary physicians.

Results:

1) Fever- associated seizures (FS) were seen in 24 patients (48%). The onset ages were; 0-1 month, 1-6 m, 6-12 m, 1-3 yrs, 3-5 y, 5-6 y and > 6 y in 3,8,13,4,0,4 and 2 patients, respectively. Those under 6 m numbered 11 (46%).The total numbers of FS were 1,2,3-4 and >=5 in 16.5.0 and 3 cases, respectively .Temperatures at the time of FS were 38 ,39,40, 41 and 42c in one,4,5,3 and 4 cases, respectively. The seizure duration was short except in 4 cases with febrile status convulsivus (FSC). These four FSC cases were considered to have epileptic encephalopathy and the outcomes were poor (1 death, 3 severe brain damage).

2) Chronic afebrile seizures (epilepsy) were seen in 7 cases (14%): Symptomatic Generalized Epilepsy in 3, Symptomatic Partial Epilepsy in one and Undetermined or unclear in 3. The age of onset was under 2 y in 6 cases. The seizure frequency was daily or monthly in 5.

Summary:

1) FS were common in CIPA and the characteristics differed from those of ordinary febrile seizures despite the good prognosis, except in FSC cases.

2) If FS persist, intensive therapy for the prevention of subsequent epileptic encephalopathy is essential.

3) The incidence of epilepsy was also higher than in the normal group.

3. Post-herpetic neuralgia in a patient with congenital insensitivity to pain and anhidrosis.

Toshiya Tomioka, Yutaka Awaya, Kenji Nihei, Kazuo Hanaoka
J.Anesthesia. 16:84-86. 2001.
We reported a patient who had been diagnosed with congenital insensitivity to pain with anhidrosis complained of itching as a sequela of herpes zoster infection. We think that this itching was a symptom of post-herpetic neuralgia.

4. Anesthesia for Patients with Congenital Insensitivity to Pain and Anhidrosis:A questionnaire Study in Japan.

Toshiya Tomioka, Yutaka Awaya, Kenji Nihei, Hiroshi Sekiyama, Shigehito Sawamura, Kazuo Hanaoka

Anesthesia&Analgesia. 94:271-274. 2002.

We previously published an article which handed anesthetic management of congenital insensitivity to pain and anhidrosis (CIPA). In this article, we showed, although lacking pain sensation, some patients do have tactile hyperesthesia. Thus, anesthetics are a necessity during operations. And we determined that since patients with CIPA have problems with thermoregulation, temperature management is a concern during the perioperative period and sufficient sedation is necessary to avoid accidental fracture. Additionally, we also showed that the use of muscle relaxants does not present a problem, malignant hyperthermia is not associated with CIPA, and the possibility of abnormalities in the autonomic nerve system must be taken into consideration. Taking these points into account, patients with CIPA can be safely managed with anesthesia.