Survey of Sixty-Four Periodic Paralyses Patients
In July of 1998 we conducted a survey of 64 self-reported medically diagnosed periodic paralysis patients, all members of the HKPP Listserv. The questionnaire underwent no formal validation process, nor was the data assessed by personnel trained in this field. The patients surveyed were drawn from several countries and across several racial/ethnic lines and backgrounds.
Patients Surveyed:
Sixty-four patients (ages 5-83) with a medical diagnosis of periodic paralysis participated in the survey. Thirty participants were female, 34 male. Most participants fell between 26-55 years of age. All participants under 25 years of age were male. The majority of the participants (84.3%) had Hypokalemic Periodic Paralysis. The remainder had Hyperkalemic Periodic Paralysis (7.8%), Paramyotonia Congenita (3.1%), Thyrotoxic PP (1.6%) or undefined variants (1.6%).
Family History:
Thirty-four percent of the participants had a known family history of periodic paralysis; family member/s in this or a previous generation who had been diagnosed with periodic paralysis. Fifty-six percent of the participants could point to family member/s in this or a previous generation with symptoms which were consistent with PP. Several families could trace the presence of symptoms back three or more generations through family records.
Age at Onset and Duration of Symptoms:
Almost half of the female participants (46.6%) reported that their symptoms started early in life, from within moments of birth to 10 years of age. A further 30% of females experienced their first episode in the second decade of life. Twenty percent of the males in this survey began experiencing symptoms in their first decade, but 57% began episodes between 11 and 20 years of age, with the peak years those between 11 and 16, when 41.2% developed symptoms. Participants had experienced episodes from 1-70 years. Female participants reported more total years with symptoms compared to male participants.
Diagnostic Process:
Female diagnostic delay from 1 day to 50 years.
Male diagnostic delay from 3 hours to 21 years.
Ninety-two percent of female participants were initially misdiagnosed. Of these 46% had their symptoms attributed to erroneous physical causes and the same number had their symptoms attributed to psychological origin. Even females with brothers and fathers who had been diagnosed and were being treated for periodic paralysis had symptoms attributed to psychological factors or described as 'emotional in origin'.
Male patients were slightly less likely to be misdiagnosed, but 37% still received an erroneous physical diagnosis and 35% had their symptoms attributed to psychological causes. Participants who were misdiagnosed or whose symptoms were attributed to psychological origins experienced significant diagnostic delay.
Periodic paralysis was confirmed in patients by a variety of methods including:
- Low potassium during paralysis with normal values during periods of strength
- Glucose/Insulin challenge
- EMG studies
- muscle biopsy
- potassium challenge
- family history and blood studies,
- positive response to potassium
- positive response to medications.
- Note: At the time of this survey none of the participants had undergone DNA testing. Several have since been genotyped. Eds
Treatment
At the time of the survey patients were receiving a variety of treatments including;
Potassium, Calcium gluconate, Diamox, Daranide, Triamterene,
Spironolactone, Albuterol/Salbutomol, Florinef, Furosemide,
Lasix, Hydrodiuril and Mexitil.
Symptoms and Presentation:
A series of questions were asked about the extent of the paralysis during episodes of generalized paralysis. Forty-three percent (43%) of our participants reported that they have experienced facial paralysis during an episode of generalized paralysis. Thirty-six percent (36%) report being unable to speak, and 27% report episodes of respiratory embarrassment. Several patients reported that they have required intubation and respiratory support during episodes.
Cardiac arrhythmia during episodes of generalized paralysis are reported by 37% of the participants. Generalized weakness which lingers after paralysis is resolved is reported in 41% of male patients and 52% of female patients.
Localized Weakness
A series of questions were asked about the incidence of episodes of localized weakness or paralysis and where these were most likely to occur. In almost all cases females were more likely to answer that they experience localized paralysis or weakness than males. Whether this is because females admit localized weakness more easily than males, or if females actually experience more localized weakness, is an intriguing question. It may offer a clue as to why it takes longer for women to be diagnosed and why more women's symptoms are attributed to psychological causes than are men's. Women's symptoms may be more subtle and more easily attributed to other causes, particularly if the woman experiences fewer episodes of generalized paralysis.
Participants answered that they experience localized weakness or paralysis most often in:
- Legs - female 73% - male 43%
- Arms - female 58% - male 38%
- Hands - female 53% - male 43%
- Hips - female 42% - male 18%
- Feet - female 38% - male 39%
- Neck - female 38% - male 23%
- Back - female 37% - male 22%
- Respiration - female 23% - male 6%
- Jaw - female 22% - male 11%
- Speech - female 20% - male 11%
- Face - female 20% - male 11%
Myotonia
Patients with HyperKPP and PMC were asked to answer questions about muscle rigidity and stiffness (myotonia), including what triggered it. The statistics are not adjusted to reflect the small size of the sample. A larger sample, or a survey taken of ONLY this group would reveal statistically more accurate information. The information itself is probably accurate, but the figures themselves are artificially low.
Repetitive use of a muscle group triggered myotonia in 23% of the females who answered and in 14% of the males. Activity of any type triggered myotonia in 13% of the respondents. These answers suggest paramyotonia in these patients. Paramyotonia is triggered by activity. Seven percent of the participants reported that activity relieved their muscle stiffness, suggesting myotonia, which responds to 'warm-up'. Thirteen percent of the participants answered that cold triggered their myotonia. Seven percent reported that myotonia could be provoked by tapping on a muscle (percussion myotonia) and seven percent reported myotonia of the eyelids.
Episode Triggers
All participants were questioned about episode triggers. Some triggers were consistently reported by approximately the same numbers of males to females. In others there were differences, which have been noted. Reported in more or less descending order were;
- Rest after activity - females 73% males 91%
- Inactivity - 70%
- Sleep - 62%
- Carbohydrates - 62% (reflects the heavily HypoKPP bias of the survey)
- Illness - 58%
- Hunger - females 58% - males 14%
- Cold - becoming chilled - 56%
- Stress - 55%
- Heat - high temperatures - females 52% - males 14%
- Large meal - 46%
- Alcohol - females 43% - males 21%
- Monthly hormonal cycle - females only - 40%
- Medications - females 30% - males 15%
- Potassium 17% (in HyperKPP patients)
Permanent Muscle Weakness
A series of questions were asked concerning the presence of permanent muscle weakness (PMW) and muscle atrophy. Twenty-seven percent of the participants reported PMW. This figure was the same for both sexes. Thirteen percent reported muscle atrophy.
Other Conditions:
We surveyed participants for incidence of the following conditions:
- Malignant Hyperthermia: 3.1%
That two of 64 patients reported that they have experienced Malignant Hyperthermia during surgery is remarkable considering that the incidence of MH is the general population is estimated at only one in 50,000 anesthetics. MH is now identified as allelic to HypoKPP and HyperKPP. Periodic paralysis patients are at greatly increased risk of developing MH during anesthesia.
Note: Since this survey was conducted in July of 1998 an additional eleven periodic paralysis patients, members of this Listserv, have reported the incidence of MH in themselves or family members during surgery, or have tested positive for MH. Susceptibility to MH among periodic paralysis patients must be considered extremely high.
- Cardiac problems: 37% (primarily arrhythmia, some cardiomyopathy)
- Neurally Mediated Hypotension or Orthostatic Hypotension: 37% of survey respondents have been diagnosed with NMH or have unusually low blood pressure. One participant in this survey reported an episode of cardiac/respiratory arrest after being given an injection of adrenaline during testing for NMH.
- Migraine: 67% Migraines are reported to often precede or accompany episodes of weakness.
- Spatial/Perceptual/Cognition problems: 55% Participants reported spatial and perceptual difficulties in conjunction with episodes. Some report temporary loss of language skills (spelling, speech, sentence construction, word recall, reading ability) with episodes. Short-term memory seems to be adversely affected during weakness, leaving patients worried about neurological effects. Cognitive problems seem to be limited to episodes, as all of our older members, though affected for many years, are in full possession of their mental faculties. Members report no diminishment of mental ability in affected family members who lived into old age.
- Fatigue and fluctuating weakness: Reported by 85% of participants.
- Pain: 95% of patients surveyed reported pain preceding or following episodes. Pain in periodic paralysis is well-described in the literature.
- Early Osteoporosis: 12% Early defined as developing before the age of 60.
- Diabetes: 10% Diabetes poses a challenge to HypoKPP patients as insulin injections may provoke paralysis within moments.