Journal of Child Neurology

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Hypokalemic Sensory Overstimulation Michael M. Segal, Gary F. Rogers, Howard L. Needleman and Catherine A. Chapman J Child Neurol 2007; 22; 1408 DOI: 10.1177/0883073807307095 The online version of this article can be found at: http://jcn.sagepub.com/cgi/content/abstract/22/12/1408

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Brief Communication

Hypokalemic Sensory Overstimulation Michael M. Segal, MD, PhD, Gary F. Rogers, MD, Howard L. Needleman, DMD, and Catherine A. Chapman, MD

Journal of Child Neurology Volume 22 Number 12 December 2007 1408-1410 © 2007 Sage Publications 10.1177/0883073807307095 http://jcn.sagepub.com hosted at http://online.sagepub.com

This report describes 2 generations of a family with symptoms of sensory overstimulation that exhibit a potassium sensitivity similar to that seen in hypokalemic periodic paralysis. The sensory overstimulation is characterized by a subjective experience of sensory overload and a relative resistance to lidocaine local anesthesia. The sensory overload is treatable with oral potassium gluconate, with onset of the therapeutic effect in ~20 minutes. The effect of potassium is reminiscent of its effect in the channelopathies underlying hypokalemic periodic paralysis, and the

resistance to lidocaine applied peripherally suggests a peripheral sensory localization to the abnormality. The phenotype overlaps with that of attention deficit disorder, raising the possibility of subtypes of attention deficit disorder that have a peripheral sensory cause and novel forms of therapy.

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rather suddenly about 20 minutes after the oral dose, “as if a shade had been pulled down.” A typical dose was 6 tablets of potassium gluconate (595 mg each; 99 mg elemental potassium). She had no school difficulties and has no signs of hyperactivity. Her symptoms of sensory overload were most common after large carbohydrate meals, meals high in NaCl, and following exercise. An acute (but less frequent) precipitant of her symptoms is episodes of diarrhea, including occasional IgG-based reactions to food similar to those described in irritable bowel syndrome.1 She suffered for many years from strong menstrual pelvic cramping and noticed in her mid40s that oral potassium supplementation blunted the menstrual pain to a dramatic degree. Several determinations of serum potassium at the time of symptoms showed potassium values in the low-normal range. Since childhood, she has been aware of a relative resistance to lidocaine dental anesthesia. Lidocaine had some effect, but anesthesia was not complete, larger than normal lidocaine doses were needed, and longer than normal times were needed to achieve acceptable local anesthesia. On several occasions, she suffered from episodes of rapid resting heart rate, often over 150 beats per minute. Almost all such episodes occurred before she began chronic potassium supplementation (typically 6 potassium gluconate [595 mg] tablets 4 times a day).

his report describes a 13-year-old boy and his 50year-old mother who have a relative insensitivity to lidocaine anesthesia and also have symptoms of sensory overstimulation that occur in a wide variety of clinical contexts.

Description of Cases Maternal History The mother began as an adolescent to take oral potassium supplements to treat leg muscle cramping, which was worst at the time of monthly menstruation. She also experienced many times a week sensory overload, both auditory (difficulty filtering out auditory signals such as extraneous conversations or background noise) and visual (a feeling of impingement by visual input with which she coped by ignoring peripheral vision). During such episodes, she had a reduced ability to receive nonverbal signals, such as those communicating social cues, and a tendency to respond in an irritable fashion to benign stimuli. In her 40s, she noticed that taking a dose of oral potassium made the sensory overload go away

From SimulConsult, Inc, Chestnut Hill, Massachusetts (MMS) and the Department of Surgery (GFR), Department of Dentistry (HLN), and Department of Neurology (CAC), Children’s Hospital, Boston, Massachusetts. Address correspondence to: Michael M. Segal, MD, PhD, SimulConsult, Inc, 27 Crafts Road, Chestnut Hill, MA 02467; e-mail: jcn@simulconsult .com. Segal MM, Rogers GF, Needleman HL, Chapman CA. Hypokalemic sensory overstimulation. J Child Neurol. 2007;22:1408-1410.

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Keywords: attention deficit disorder; sodium channel; hypokalemic periodic paralysis

Child’s History At age 9 years, the boy’s parents noticed that he often became fatigued and very irritable after meals. On questioning during one prominent episode, he described some


Hypokalemic Sensory Overstimulation / Segal et al

minor foot cramping, and based on his mother’s experience with leg cramping, oral potassium supplementation was tried and reported to be helpful. Over the next several years, it became apparent that he was very distractible in the classroom setting and had considerable difficulty completing school assignments at home as well, despite the assignments posing little intellectual challenge to him. Carelessness and poor organization in school work and impulsivity were also noted. Based on the mother’s experience with sensory overstimulation, oral potassium supplementation was tried on a more chronic basis, with considerable improvement as judged by family and school. The symptoms of sensory overload were most common after large carbohydrate meals, meals high in NaCl, and following exercise. In addition, various other problems associated with attention deficit disorder2,3 were noted, including oppositionalism, anxiety, and poor handwriting. At age 12 years, the boy was assessed by a behavioral neurologist. Upon review of questionnaire data from parents and teachers in combination with a structured diagnostic interview, it was concluded that his profile was consistent with attention deficit disorder without hyperactivity to a mild degree. His academic performance was not seriously affected because of his superior cognitive ability, characterized in psychometric testing (Wechsler Intelligence Scale for Children—4th edition: Verbal Comprehension 130, Perceptual Reasoning 117, Working Memory 132, Processing Speed 106; no Full-Scale value was applicable because of the magnitude of the discrepancy between composite scores). The Conners Parent Rating Scale (CPRS-48): Short Version revealed a hyperactivity index T score of 70. The Conners Teacher Rating Scale (CTRS-28): Short Version revealed hyperactivity indices from 4 teachers with T scores equal to 77, 79, 82, and 82. The diagnosis of Attention Deficit Disorder without Hyperactivity was made based on the written data and descriptive information provided by the parents and teachers on the open-ended sections of the questionnaires and interview. At age 11 years (weight 33 kg), he was given lidocaine local anesthesia for elective removal of an ingrown toenail on the large toe of 1 foot. Although there was a small amount of purulent fluid, the toe showed no signs of more serious infection. Lidocaine (1%, without epinephrine) was given in repeated injections totaling 15 mL because the patient reported continued sensation. He could document the inadequacy of anesthesia by reporting accurately the location of forceps touches to the toe under conditions in which he could not see his toe. His mother’s history of difficulty with lidocaine dental anesthesia was not known at that time to the medical personnel or to any members of the family other than the mother, and the mother was not present for the procedure. Whenever injured, he reported discomfort out of proportion to that reported by other children. On 2 occasions

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following minor trauma, he reported inability to move the injured limb, which resolved within hours. At age 9 years, after being hit in the eye by a softball, he reported inability to see from that eye, but monocular testing documented normal vision in each eye at a time at which he still reported monocular blindness (tested using a Titmus T-2s Vision Screener [Titmus Optical, Petersburg, Va] that occluded eyes one at a time in a way not obvious to the patient), and pupillary responses were normal. The report of visual disturbance resolved within 2 hours. At age 13 years, he was referred to his pediatric dentist by his orthodontist for extraction of the maxillary right primary canine tooth, first molar, and second molar because of transposition of his maxillary right permanent canine and first premolar. The planned extractions presented a management issue because of his history and his mother’s history of relative insensitivity to lidocaine. He had the 3 teeth extracted without significant pain using the following regimen: 1. Three doses of 6 potassium glutamate (595 mg) tablets each in the hours between waking and the procedure (5 hours, 2.5 hours, and minutes before) 2. 1.8 mL of infiltrative local anesthesia using articaine hydrochloride 4% with epinephrine 1:100:000 3. Administration of inhalation nitrous oxide/oxygen (40%/60%)

Discussion Both patients display 2 abnormalities suggestive of sensory overstimulation: a relative resistance to lidocaine local anesthesia and reports of sensory overload. The sensory overload includes both a perceived sensory overload characteristic of attention deficit disorder4 and unusually severe experiences of pain. Although much of the data in these case reports come from self-reports of sensory experiences, the boy’s ability to describe the details of sensory stimulation to his nominally anesthetized toe despite many injections of lidocaine appears to be objective evidence of an abnormality in sensory input. The other striking feature of these 2 patients is that the sensory overload is alleviated by oral potassium supplementation. The triggers for the sensory overload described by both patients correspond to those described in hypokalemic periodic paralysis (exercise, NaCl, and large carbohydrate meals5) and other circumstances known to lower serum potassium (menstruation and diarrheal illnesses). As in hypokalemic periodic paralysis, we did not find any evidence that potassium levels are lower than those of normals; instead, it seemed that symptoms occur during normal physiological fluctuations of serum potassium that would not cause symptoms in the average person. The symptomatology is very different from hypokalemic periodic paralysis. The best clue to the anatomical localization of this disorder seems to come from the relative resistance to


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Journal of Child Neurology / Vol. 22, No. 12, December 2007

lidocaine local anesthesia. Because lidocaine injected peripherally acts on sodium channels in peripheral sensory pathways, this suggests an abnormality in this disorder expressed in a peripheral sensory pathway. Although attention deficit disorder is often presumed to have a central basis,6 the cases presented here suggest that overstimulation in a peripheral sensory pathway is another mechanism that could, in some forms of attention deficit disorder, explain the sensory overstimulation. Hypokalemic periodic paralysis results typically from mutations in ion channel genes. The mutations are chiefly in calcium channel genes or sodium channel genes, but a few cases may be due to potassium channel gene mutations.5 Channelopathies due to mutations of sodium channels have been described also in hyperkalemic periodic paralysis,5 the cardiac long QT syndrome,7 several forms of epilepsy,8 and the intense pain syndrome, SCN9A-related inherited erythromelalgia.9 The family described here may have another channelopathy with localization to peripheral sensory pathways and a phenotype distinct from that of channelopathies described previously. Understanding of the clinical picture in these patients was helpful in designing a protocol for dental anesthesia. Instead of using the sodium channel antagonist lidocaine alone, using the combination of the more diffusible sodium channel blocker articaine10-13 and vigorous potassium supplementation appears to have produced local anesthesia that was much more effective than the anesthesia produced by lidocaine alone. (Nitrous oxide/oxygen analgesia was added to both reduce the boy’s anxiety and raise his pain threshold.) By taking a family history of insensitivity to local anesthesia, dentists can plan appropriate anesthesia and possibly uncover sensory symptoms with expression outside of dentistry. Attention deficit is a finding present in many disorders. As in epilepsy, where an estimated 1000 genes can produce seizures if mutated,14 it is likely that abnormalities in many different genes can produce the finding of attention deficit. The standard treatment for attention deficit disorder using drugs that act on biogenic amine neurotransmission has led to a presumption that attention deficit disorder involves disturbances in biogenic amine neurotransmission.6 The existence of individuals with attention deficit disorder ascribable to a peripheral channelopathy would add a different mechanism of action to consider. An ability to treat attention deficit disorder in some individuals with oral potassium supplementation could be a useful treatment option, particularly in light of recent concerns about side effects of drugs targeting biogenic amine neurotransmission.15

Acknowledgments We thank Drs Isabelle Rapin and Anne Louise Oaklander for their comments on earlier versions of this manuscript.

Dr Segal’s laboratory studies of sodium channel overactivity in epilepsy16 were supported by the Esther and Joseph Klingenstein Fund. The observations are clinical ones from physicians who saw the patients in the Boston area, not paid for by any grants. The work has not been presented in abstract form or in talks. The laboratory work was done by Dr Segal in his lab at Children’s Hospital, Boston, in the 1990s. Conflicts of interest or commercial support: none.

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