Abstracts: Research on Treatment of Seizure Cause
(Western doctors who treated absence spells and seizures
with breathing techniques)
Magarian GJ, Olney RK, Absence spells. Hyperventilation
syndrome as a previously unrecognized cause, Am J Med. 1984
Absence spells in adults have been recognized in association with
disorders of excessive somnolence, transient ischemia of the temporal
lobes, and seizure disorders. A 66-year-old man who presented with a
history of absence spells for more than 20 years is described. After diagnosis of a
hyperventilation syndrome without an associated seizure disorder,
educational and behavioral therapy without the use of medication has
produced a long, continuing remission of these spells. The
hyperventilation syndrome continues to present in many ways, often
without recognition by physicians for prolonged periods. The case
presented exemplifies this problem and may be the first report of
absence spells caused by hyperventilation.
Bruno-Golden B, Holmes GL, Hyperventilation-induced seizures in
mentally impaired children, Seizure. 1993 Sep;2(3):229-33.
Boston Neurobehavioral Institute, Harvard Medical School, Children's
Hospital, MA 02115.
Two children with profound development delay and medically intractable
seizures were found to have hyperventilation-induced seizures.
Following detection of this precipitating factor the parents, teachers
and caretakers were taught to modify the childrens' breathing when they
began to hyperventilate. In
both patients this technique resulted in a dramatic decrease in seizure
Fried R, Rubin SR, Carlton RM, Fox MC, Behavioral control of
intractable idiopathic seizures: I.
Self-regulation of end-tidal carbon dioxide, Psychosom Med. 1984
Eleven women and seven men with moderate to severe chronic
hyperventilation and idiopathic seizures refractory to therapeutic
serum levels of anticonvulsant medication were given diaphragmatic
respiration training with percent end-tidal CO2 biofeedback. The
training had a rapid correcting effect on their respiration, making it
comparable to that of 18 asymptomatic control subjects. Ten of the
seizure-group subjects were in the study at least 7 months and
following treatment, 8 showed EEG power spectrum "normalization",
restoration of cardio-respiratory synchrony (RSA), and their seizure frequency and
severity were significantly reduced.
Medical references for calming CO2 effects on brain cells
“Studies designed to determine the
effects produced by hyperventilation on nerve and muscle have been consistent in
their finding on increased irritability” Brown EB,
Physiological effects of hyperventilation, Physiological Reviews 1953 October,
Vol. 33 No. 4;
"Conclusions. Many cells clearly reacted to even small changes in Pco2
(e.g. 4 mm Hg). Moderate doses of CO2 led to both excitation and depression;
typically there was an initial phase of excitation during the rise in PCO2,
a subsequent longer period of depression, and some sharp excitation during
the fall of PCO2." Krnjevic K,
Randic M and Siesjo B, Cortical CO2 tension and neuronal
excitability, Journal of Physiology 1965, No. 176: p.105-122.
"Orthodromically evoked compound action potentials ('population
spikes') were depressed in hypercapnia and increased in hypocapnia." Balestrino M, Somjen GG, Concentration of carbon dioxide, interstitial pH and
synaptic transmission in hippocampal formation of the rat, Journal of Physiology,
1988, No. 396: p. 247-266.
"Hyperventilation leads to spontaneous
and asynchronous firing of neurons" Huttunen J,
Tolvanen H, Heinonen E, Voipio J, Wikstrom H, Ilmoniemi RJ, Hari R, Kaila K,
Effects of voluntary hyperventilation on cortical sensory responses.
Electroencephalographic and magnetoencephalographic studies, Experimental Brain Research
1999, Vol. 125 No. 3: p. 248-254.
Neuron. 2005 Dec 22;48(6):1011-23.
Adenosine and ATP link PCO2 to cortical excitability via pH.
Dulla CG, Dobelis P, Pearson T, Frenguelli BG, Staley KJ, Masino SA.
Neuroscience Program, Department of Neurology, University of Colorado Health
Sciences Center, Denver, Colorado 80262, USA.
In addition to affecting respiration and vascular tone, deviations from
normal CO(2) alter pH, consciousness, and seizure propensity. Outside
the brainstem, however, the mechanisms by which CO(2) levels modify neuronal
function are unknown. In the hippocampal slice preparation, increasing
CO(2), and thus decreasing pH, increased the extracellular concentration of
the endogenous neuromodulator adenosine and inhibited excitatory synaptic
transmission. These effects involve adenosine A(1) and ATP receptors and
depend on decreased extracellular pH. In contrast, decreasing CO(2) levels
reduced extracellular adenosine concentration and increased neuronal
excitability via adenosine A(1) receptors, ATP receptors, and ecto-ATPase.
Based on these studies, we propose that CO(2)-induced changes in neuronal
function arise from a pH-dependent modulation of adenosine and ATP levels.
These findings demonstrate a mechanism for the bidirectional effects of
CO(2) on neuronal excitability in the forebrain.
Br J Anaesth. 1972 Nov;44(11):1128-32.
Effects of acute hypocapnia and hypercapnia on neuromuscular transmission
and on monosynaptic spinal reflex in wakeful man.
Higashi H, Kano T, Shimoji K, Morioka T, Sances A.
The effects of both acute hypocapnia and hypercapnia on neuromuscular
transmission (NMT) and monosynaptic spinal reflex (MSR) in conscious
subjects were studied by observing the averaged evoked electromyogram. The
M-wave amplitude increased to 165 ~+mn~ 25 % (mean ~+mn~ standard error) during
acute hypocapnia with an end expiratory carbon dioxide concentration of 2.5
~+mn~ 0.2 vol.% and decreased to 73 + 7% during acute hypercapnia with an
expiratory concentration of 6.8 ~+mn~ 0 . 1 vol.%, in comparison with the
control value. The H-wave amplitude increased to 226 ~+mn~ 8 2% during acute
hypocapnia and decreased to 85 ~+mn~ 9% during acute hypercapnia in comparison
with the control value. These results indicate that both NMT and MSR in
conscious man are facilitated by acute hypocapnia, and that NMT is inhibited
by acute hypercapnia. However, the effect of acute hypercapnia on MSR
could not be ascertained only by the observation of the H reflex in these
References and quotes (Overbreathing and irregular breathing
EC, Camfield PR, Gordon KE, Camfield CS, Dooley JM, Hanna BD, Will a
critical level of hyperventilation-induced hypocapnia always induce an
absence seizure? Epilepsia. 1996 May;37(5):459-62.
Paediatrics, Dalhousie University Medical School, Izaak Walton Killam
Hospital for Children, Halifax, Nova Scotia, Canada.
We wished to
determine if the degree of hypocapnia correlates with increased
frequency of absence seizures and if there is a critical pCO2 at which
absence seizures are reliably provoked. Twelve untreated children with
newly diagnosed absence epilepsy were continuously monitored by EEG and
end-expiratory CO2 recording during quiet respiration and
hyperventilation (to absence seizure or exhaustion) while breathing
four gas mixtures: (a) room air, (b) 100% O2, (c) 4% CO2 in room air,
or (d) 4% CO2 + 96% O2). In quiet respiration, a reduction in number of
spike and wave bursts and total seconds of spike and wave was noted in
children breathing supplemental CO2 (gases c and d vs. gases a and b),
p < 0.05. Supplemental O2 had no effect. Eight subjects had absence
seizures elicited with each trial of hyperventilation. All subjects had
their own critical pCO2, ranging from 19 to 28 mmHg. Three children had
no seizures, two despite hypocapnia to pCO2 of 19 and 21 and 1 who
achieved a pCO2 of only 25. In 1, absence seizures were provoked in
only six of nine hyperventilation trials to pCO2 of 17-23. In 67% of subjects, absence seizures were reliably provoked by hypocapnia.
Critical pCO2 varied among children with absence. Determination of
whether variation in sensitivity to hypocapnia may be helpful in
determining response to antiepileptic drugs (AEDs) or remission of
seizures will require further study.
J, Vignal JP, Baumann C, Anxionnat JF, Muresan M, Vespignani H,
Maillard L, Effect of hyperventilation on seizure activation:
antiepileptic drug tapering, J Neurol Neurosurg Psychiatry. 2010 Jun
20. [Epub ahead of print]
Service de Neurologie, Centre Hospitalier Universitaire de Nancy, Nancy, France.
... Discussion. The findings confirm that hyperventilation is efficient to activate epileptic seizures in epileptic patients
referred for long-term video-EEG monitoring and that this activating
effect is mainly related to the potentiating effect of AED
Zhang Y, Yang Z, Liu X, Sun H, Qin J, Wu X, Liang J, Childhood absence
epilepsy: Electroclinical features and diagnostic criteria, Brain Dev.
2010 Apr 6. [Epub ahead of print]
Department of Pediatrics, Peking
University First Hospital, No. 1, of Xian Men Street, Xicheng District,
Beijing 100034, PR China; Bayi Children's Hospital Affiliated to
General Hospital of Beijing District, PLA 100710, PR China.
To analyze the electroclinical features of children with childhood
absence epilepsy (CAE) and discuss the diagnostic criteria for CAE.
Methods: The video-electroencephalogram (VEEG) database in our hospital
was searched using "absence seizures" and "3-Hz generalized spike and
waves (GSW)" as key-words. Other epileptic syndromes with typical
absence seizures were carefully excluded. Children meeting the CAE
diagnostic criteria of the International League Against Epilepsy (ILAE)
in 1989 were further evaluated with the diagnostic criteria proposed by
Panayiotopoulos in 2005. Results: Totally 37 children met the 1989 ILAE criteria of CAE.
The onset age of absence seizures ranged from 3 to 11years. All
patients had frequent absence seizures (5-60 times per day). Two
patients (5.4%) had generalized tonic-clonic seizures. Hyperventilation induced absences in all patients...
Yang ZX, Liu XY, Qin J, Zhang YH, Wu Y, Jiang YW, [Clinical and electroencephalographic characteristics of epilepsy with
myoclonic absences] [Article in Chinese], Zhonghua Er Ke Za Zhi. 2009
Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
Epilepsy with myoclonic absences (EMA) is a type of childhood epilepsy
characterized by a specific seizure type, i.e. myoclonic absences (MA).
This study aimed to investigate the clinical and electrophysiological
characteristics of EMA. METHOD: Video-EEG monitoring was carried out in
6 patients with EMA, and 2 of them were examined with simultaneous
deltoid muscle surface electromyogram (EMG). The clinical and EEG
characteristics, treatment and prognoses of EMA were analyzed. RESULT:
Of the 6 patients, 3 were female, and 3 were male. The age of onset was
from 2 years and 3 months to 11 years (average 5 years and 2 months).
MA was the sole seizure type in 5 patients. One patient presented
generalized tonic clonic seizures (GTCS) at the onset and then switched
to MA. The manifestations of MA
included an impairment of consciousness of variable intensity, rhythmic
myoclonic jerks with evident tonic contraction mainly involving the
upper extremities, a deviation of head and body to one side or
asymmetrical jerks observed in some cases, a duration ranging from 2 to
30 s, an abrupt onset and termination, a high frequency of attacks, at
least several times to over 30 times per day, and easily provoked by
Yang Z, Liu X, Qin J, Jiang Y, Neck myoclonia with absence seizures: report of 3 cases, J Child Neurol. 2009 Aug;24(8):1026-9.
Department of Pediatrics, Peking University First Hospital, Beijing, People's Republic of China.
seizures associated with myoclonic phenomena can be seen in typical
absences, myoclonic absences, eyelid myoclonia, and perior al
myoclonia, all of which have diagnostic electroclinical features. The
authors report 3 patients who encountered prominently rhythmic neck
myoclonias with and without absences (loss of awareness). The
descriptive symptoms of attacks by witnesses were head shaking or
turning repeatedly instead of absences. The seizures were induced by hyperventilation in all 3 cases...
AM, Arbogast PG, Abou-Khalil BW, Utility of daily supervised
hyperventilation during long-term video-EEG monitoring, J Clin
Neurophysiol. 2009 Feb;26(1):17-20.
Department of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee, USA. [email protected]
Hyperventilation (HV) is most effective in activation of generalized absence seizures during routine EEG studies...
J ECT. 2008 Sep;24(3):195-8.
Moderate hyperventilation prolongs electroencephalogram seizure duration of the first electroconvulsive therapy.
Sawayama E, Takahashi M, Inoue A, Nakajima K, Kano A, Sawayama T, Okutomi T, Miyaoka H.
Department of Psychiatry, Kitasato University School of Medicine, Sagamihara, Japan. [email protected]
it is controversial that seizure duration can influence the efficacy of
electroconvulsive therapy (ECT), a missed or brief seizure is
considered less effective ECT. Of the background in the practice of
ECT, hyperventilation may augment the seizure duration. To elucidate
these hypotheses, we performed double-blind randomized controlled trial
for 19 patients. They were divided into 2 groups, according to the
end-tidal pressure of carbon dioxide (ETCO2): The moderate
hyperventilation group with ETCO2 of 30 mm Hg and the normal
ventilation group with ETCO2 of 40 mm Hg. ECT was performed under
general anesthesia with propofol and suxamethonium. During ECT
electroencephalogram (EEG) and electromyogram were recorded. The Global
Assessment of Functioning scores were also analyzed before and after 6
sequential ECT. The moderate
hyperventilation group showed a significant increase in EEG seizure
duration in the first treatment compared with the normal ventilation
group (P < 0.05)...
W, Giagante B, Saizar R, D'Alessio L, Oddo S, Consalvo D, Saidón P,
Kochen S, Clinical features and prognosis of nonepileptic seizures in a
developing country, Epilepsia. 2001 Mar;42(3):398-401.
Epilepsy Center, Department of Neurology, Ramos Mejía Hospital, and
CONICET, Buenos Aires, Argentina. [email protected]
To determine the predictive value of clinical features and medical
history in patients with nonepileptic seizures (NESs). METHODS: One
hundred sixty-one consecutive ictal video-EEGs were reviewed, and 17
patients with 41 NESs identified. NES diagnosis was defined as
paroxysmal behavioral changes suggestive of epileptic seizures recorded
during video-EEC without any electrographic ictal activity. Clinical
features, age, sex, coexisting epilepsy, associated psychiatric
disorder, social and economic factors, delay in reaching the diagnosis
of NES, previous treatment, and correlation with outcome on follow-up
were examined. RESULTS: The study population included 70% female
patients with a mean age of 33 years. Mean duration of NESs before
diagnosis was 9 years. Forty-one percent had coexisting epilepsy. The most frequent NES clinical features were tonic-clonic mimicking movements and fear/ anxiety/ hyperventilation...
Paediatr Drugs. 2001;3(5):379-403.
Treatment of typical absence seizures and related epileptic syndromes.
of Clinical Neurophysiology and Epilepsies, St Thomas' Hospital,
London, England. [email protected]
absences are brief (seconds) generalised seizures of sudden onset and
termination. They have 2 essential components: clinically, the
impairment of consciousness (absence) and, generalised 3 to 4Hz
spike/polyspike and slow wave discharges on electroencephalogram (EEG).
They differ fundamentally from other seizures and are pharmacologically
unique. Their clinical and EEG manifestations are syndrome-related.
Impairment of consciousness may be severe, moderate, mild or
inconspicuous. This is often associated with motor manifestations,
automatisms and autonomic disturbances. Clonic, tonic and atonic
components alone or in combination are motor symptoms; myoclonia,
mainly of facial muscles, is the most common. The ictal EEG discharge
may be consistently brief (2 to 5 seconds) or long (15 to 30 seconds),
continuous or fragmented, with single or multiple spikes associated
with the slow wave. The intradischarge frequency may be constant or may
vary (2.5 to 5Hz). Typical absences are easily precipitated by hyperventilation in about 90% of untreated patients...
F, Puligheddu M, Giagheddu M, Cossu G, Piga M, Correlation between
cerebral perfusion and hyperventilation enhanced focal spiking
activity, Epilepsy Res. 2000 Jun;40(1):79-86.
Neurology and Department of Nuclear Medicine, Faculty of Medicine,
University of Cagliari, Via Ospedale, 54 09100, Cagliari, Italy.
... Hyperventilation (HPV) represents a well established EEG activation procedure aimed at enhancing epileptiform discharges...
Clin Electroencephalogr. 1993 Jan;24(1):1-5.
Transcranial magnetic stimulation (TMS) of the brain in patients with mesiotemporal epileptic foci.
Steinhoff BJ, Stodieck SR, Zivcec Z, Schreiner R, von Maffei C, Plendl H, Paulus W.
Department of Neurology, Ludwig-Maximilians-Universität, Munich, Germany.
magnetic stimulation (TMS) of the human brain is mainly used for the
diagnosis of diseases with disturbed central motor conduction. Recent
studies revealed controversial results concerning the possibility of a
TMS-induced specific activation of epileptogenic foci in patients with
localization-related epilepsies, which would make TMS an additional
diagnostic tool for the presurgical localization of the primary
epileptogenic zone. We applied TMS to 19 patients with complex-partial
seizures and investigated its effects and safety. In 12 patients we
performed TMS during scalp electroencephalogram (EEG) recordings. The
remaining 7 patients with localization-related epilepsies of mesiobasal
limbic seizure origin underwent EEG with additionally implanted
foramen-ovale-electrodes (FOE). We did not notice any significant spike
activation and even observed bilateral reduction of epileptic activity
in some patients. On the contrary, hyperventilation induced a marked activation of the epileptic focus.
Our findings support that TMS is safe since adverse effects did not
occur. However, due to possible safety hazards, TMS in epileptic
patients still requires cautious application until more data will be
Bergsholm P, Gran L, Bleie H, Seizure duration in unilateral electroconvulsive therapy. The effect of
hypocapnia induced by hyperventilation and the effect of ventilation
with oxygen, Acta Psychiatr Scand. 1984 Feb;69(2):121-8.
duration in unilateral electroconvulsive therapy (ECT) was recorded by
means of EEG in an intraindividual comparison under different alveolar
O2- and CO2-concentrations. Hypocapnia
induced by hyperventilation to an alveolar CO2-concentration of 2% (2
kPa) resulted in a highly significant increase in seizure duration
compared to a normal CO2 of 5%, when the alveolar O2-concentration was
constant at 92%. Oxygen ventilation to an alveolar O2-concentration of
92% gave no significant increase in seizure duration compared to 15%,
obtained by ventilation with air, when the CO2-concentration was kept
constant at 5%. Seizure duration seems to augment progressively with
decreasing alveolar CO2-concentration.
Neurol Neurochir Pol. 1981 Sep-Dec;15(5-6):545-52.
[Effect of physical exertion on seizure discharges in the EEG of epilepsy patients]
[Article in Polish]
Horyd W, Gryziak J, Niedzielska K, Zielinski JJ.
purpose of this study was establishing the effect of moderate exercise
on EEG tracings in young epileptics. The model of graded exercise was
15-minute work on a cycle ergometer. The effect of the exercise on the
pattern of simultaneously recorded EEG was compared with the effect of
3-minute hyperventilation. After testing a control group of 20 young
subjects without evidence of organic brain damage or with this damage
causing no epilepsy another group of 43 epileptics was studied. In none
of these patients the intensity of changes in EEG increased during the
exercise but evident EEG differences could be detected during different
stages of the exercise in 28 patients with significant generalized
discharges. It was found that during the exercise in nearly all
patients the number of discharges decreased while during
hyperventilation it increased. In 10 patients in this group a repeated
rise in the number of discharges was observed immediately after the
exercise which was connected usually with greater fatigue after the
exercise. In the light of these results the authors conclude that moderate exercise inhibits rather seizure activity in EEG contrary to hyperventilation which increases these changes.
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