Kathryn Davis, MD, MTR, director of the Epilepsy Monitoring Unit and assistant professor of Neurology, explained how a startup is using the brain waves of large numbers of people to assess an individual’s risk of seizure disorders more quickly and accurately. She emphasized that those tests aren’t definitive — the scans don’t always show anything unusual in people who do have epilepsy.
Now, a startup is using a database of EEG records from people with and without epilepsy, to create a computer model that builds a network of interactions between the signals produced by the electrodes placed on the head to measure brain activity. The software uses the model to generate a risk score that can help a clinician to assess an individual’s risk of epilepsy.
The symptoms that many people associate with someone having an epileptic seizure — losing consciousness, biting the tongue or even briefly ceasing to breathe — would make it seem that diagnosing this condition would be a simple matter.
But diagnosis is a tricky process that usually takes months — and might never be definitive. People with epilepsy describe their diagnostic journey as “long, confusing, unclear and uncertain”, says John Terry, a mathematician at the University of Birmingham, UK
Terry is co-founder and managing director of Neuronostics in Bristol, UK, a start-up that aims to shorten this journey. The company’s patented software, BioEP, analyses electroencephalography (EEG) recordings of brain activity that are routinely collected during the first appointment with a neurologist. It can identify epilepsy from a single recording, with a similar sensitivity to that of clinicians who conduct numerous tests over many months, says Terry.
The implications are enormous. More than 65 million people, nearly 1% of the global population, have epilepsy, and the condition has serious associated risks. Quicker and more reliable diagnosis could lead to earlier treatment and could substantially reduce the potentially severe impact on people’s quality of life.
“This technology could be a game changer for epilepsy diagnosis,” says Exeter-based Simon Privett, an epilepsy-awareness advocate at the UK charity Epilepsy Action, who has worked closely with Terry and his team.
Beyond the standard scans
Epileptic seizures are driven by unusual electrical activity in the brain. A diagnosis is made on the basis of clinical history, and EEG and magnetic resonance imaging (MRI) scans help to confirm the diagnosis, says Kathryn Davis, a neurologist specializing in epilepsy at the University of Pennsylvania in Philadelphia.
But Davis emphasizes that those tests aren’t definitive — the scans don’t always show anything unusual in people who do have epilepsy.
Among people who have had a seizure but whose scans don’t show unusual activity, the risk of a second seizure is only around 30%, Davis says. She usually doesn’t prescribe anti-epileptic drugs at that point. “I’m just counselling them to wait and see if you have another potentially life-threatening event,” she says. “And if you do, then we’ll treat you. That’s an extremely common scenario.”
Currently, clinicians examine EEG readouts and look for precursors of seizures such as spikes in activity or brief bursts of unusual pathological activity. They also look for seizures. “The trouble is that these are all quite rare events,” Terry says. So clinicians usually begin a process to eliminate psychological or physical causes of the seizures — monitoring people for progressively longer periods of time, and upping stresses that can trigger seizures, such as lack of sleep, to pick up signals of epilepsy.
Terry and his collaborators at Neuronostics instead use 20 seconds of seizure-free data from a routine EEG scan. Using a database of EEG records from people with and without epilepsy, the researchers have created a computer model that has built a network of interactions between the signals produced by the electrodes placed on the head to measure brain activity, called EEG channels1 (see ‘Simulating seizure risk’). This model, Terry explains, describes “transitions between background states in the brain that are apparently healthy, and seizure-like states that are apparently pathological”. The Neuronostics software uses the model to generate a risk score that can help a clinician to assess an individual’s risk of epilepsy.
Simulating seizure risk
With a conventional evaluation of an initial EEG scan, a clinician can correctly diagnose roughly 25% of people with epilepsy, according to Terry. Unpublished research with the Neuronostics model shows that it performs much better, detecting epilepsy in 60% of those who do have the condition, and making the right assessment in 87% of cases.
Accelerating the diagnosis of epilepsy has two major advantages. First, it avoids the need for long-term testing, and the associated disruption for those being examined. Second, it reduces the number of seizures a person is likely to have — delays in diagnosis and treatment mean that seizures will keep happening, and, generally, the more seizures someone has, the more likely they are to have more.
If fully validated, the ability of Neuronostics’ method to outperform clinicians’ interpretations of initial EEGs could prove very helpful for diagnosis, says Davis.
Delivering on diagnostics
Neuronostics’ system has been long in gestation. Terry and his colleagues first reported2 the method in 2012. Terry then discussed the research with a commercial technology specialist at the University of Exeter (where Terry was then based) who was impressed with the technology and its potential impact. The university applied for patent protection and, in 2018, aided the company’s formation. It also helped to secure a series of UK government grants — most recently, two awards totalling £870,000 (US$1.2 million) in September 2020 from the National Institute for Health Research.
In March, the company raised £300,000 in a seed round of financing. It now has four full-time employees and is hiring, among other roles, a head of marketing.
Neuronostics estimates there is a potential market of 3.5 million EEGs annually in the United States and Europe, and it plans to charge a per-use fee of $400 in the United States and the equivalent of $280 in the United Kingdom (the fee is lower in the United Kingdom because of requirements under its government sponsorship). The company received regulatory approval for BioEP in Europe and the United Kingdom in May, with expansion to the United States planned for late 2022.
The diagnosis of epilepsy might not, however, prove to be the software’s most valuable offering. The start-up also sees potential for determining prognosis for people taking epilepsy treatments, says mathematician Wessel Woldman at the University of Birmingham, who is co-founder and scientific director at Neuronostics. Indeed, although some neurologists remain sceptical about EEG analysis for diagnosis, “when it comes to prognosis, there’s a lot more of a realization that computer-assisted methods could really contribute something meaningful”, Woldman says.
About one-third of people diagnosed with epilepsy get no benefit from any available drug. For the remaining two-thirds, finding the right treatment can take months. Neuronostics analyses might allow clinicians to observe the effects of a medication much more quickly, which could cut down on seizures and minimize the use of medications with significant side effects, Woldman says. He is collaborating with clinicians at St Vincent’s Hospital in Fitzroy, Australia, to test the approach. Very early results are encouraging, he says.
Neuronostics is also developing a smartphone app called ConnectEP that works with a new generation of inexpensive, gel-free wireless EEG headsets designed for home use. The resulting data won’t be clinical-grade but could still prove highly useful to neurologists, Terry says. The company hopes to release the app by the end of 2021.
Later generations of ConnectEP could also produce useful short-term forecasts of risk of seizures — an exciting possibility, says Privett, who is involved in testing prototypes. Overall, Privett says, the potential impact of Neuronostics technology for people with epilepsy is huge.
As it commercializes its technology, Neuronostics is maintaining its tight focus on feedback from all the stakeholders in epilepsy treatment — especially those with the condition. “Our ethos”, says Terry, “is to ensure that our models and experiments and clinical work develop very closely together.”
Kathryn Davis, MD, MTR, mkurugenzi wa Kitengo cha Ufuatiliaji wa Mshtuko na profesa msaidizi wa Neurolojia, alielezea jinsi startup inavyotumia mawimbi ya ubongo ya idadi kubwa ya watu kutathmini hatari ya mtu binafsi ya matatizo ya mshtuko haraka na kwa usahihi. Alisisitiza kwamba vipimo hivyo si vya uhakika - uchunguzi huo haionyeshi sikuzote jambo lolote lisilo la kawaida kwa watu walio na kifafa. Kampuni ya startup ya New York inatumia database ya rekodi za EEG kutoka kwa watu wenye na wasio na kifafa, kuunda mfano wa kompyuta ambao hujenga mtandao wa mwingiliano kati ya ishara zinazozalishwa na elektroni zilizowekwa kwenye kichwa ili kupima shughuli za ubongo. Programu hutumia mfano huo kutengeneza alama ya hatari ambayo inaweza kusaidia daktari kutathmini hatari ya mtu binafsi ya kifafa. Dalili ambazo watu wengi huhusianisha na mtu mwenye kifafa - kupoteza fahamu, kuumwa ulimi au hata kuacha kupumua kwa muda mfupi - zingefanya ionekane kwamba ni rahisi kugundua ugonjwa huo. Lakini utambuzi ni mchakato mgumu ambao kwa kawaida huchukua miezi <unk> na huenda usiwe wa mwisho kamwe. "Watu wenye kifafa huelezea safari yao ya utambuzi kama ""mrefu, yenye kuchanganyikiwa, isiyo wazi na isiyo na uhakika,"" anasema John Terry, mwanahisabati katika Chuo Kikuu cha Birmingham, Uingereza, na mwanzilishi mwenza na mkurugenzi mtendaji wa Neuronostics huko Bristol, Uingereza, kuanza ambayo inakusudia kufupisha safari hii." Programu ya kampuni hiyo ya BioEp inachunguza rekodi za electroencephalography (EEG) za shughuli za ubongo ambazo hukusanywa mara kwa mara wakati wa mkutano wa kwanza na mtaalamu wa neva. "Teri anasema, ""Inaweza kutambua ugonjwa wa kifafa kutokana na rekodi moja, kwa utambuzi sawa na ule wa madaktari ambao hufanya vipimo vingi kwa miezi mingi.""" Matokeo ni makubwa sana. Zaidi ya watu milioni 65, karibu 1% ya idadi ya watu duniani, wana kifafa, na hali hiyo ina hatari kubwa zinazohusiana. Uchunguzi wa haraka na wa kuaminika zaidi unaweza kuongoza kwa matibabu ya mapema na inaweza kupunguza athari mbaya kwa ubora wa maisha ya watu. "Teknolojia hii inaweza kuwa mabadiliko ya mchezo kwa utambuzi wa kifafa, ""anasema Simon Privett, anayeishi Exeter, mtetezi wa ufahamu wa kifafa katika shirika la misaada la Uingereza la Epilepsy Action, ambaye amefanya kazi kwa karibu na Terry na timu yake." Zaidi ya uchunguzi wa kawaida Mshtuko wa kifafa husababishwa na utendaji wa kawaida wa umeme katika ubongo. Uchunguzi wa EEG na MRI (Magnetic Resonance Imaging) huonyesha kwamba ugonjwa huo ni wa kawaida, anasema Kathryn Davis, mtaalamu wa magonjwa ya neva katika Chuo Kikuu cha Pennsylvania huko Philadelphia. Lakini Davis anasisitiza kwamba vipimo hivyo si vya uhakika - uchunguzi huo haionyeshi sikuzote jambo lolote lisilo la kawaida kwa watu walio na kifafa. "Wakati wa watu ambao wamekuwa na mshtuko wa akili lakini ambao uchunguzi wao haujionyesha shughuli isiyo ya kawaida, hatari ya mshtuko wa pili ni karibu 30% tu, ""alisema Davis." Kwa kawaida yeye haagizi dawa za kuzuia kifafa wakati huo. "Ninawashauri tu wasubiri na kuona kama una tukio jingine linaloweza kuhatarisha maisha", anasema. <unk>Na kama unafanya, basi sisi <unk>tawatunza. Kwa sasa, madaktari huchunguza matokeo ya EEG na kutafuta dalili za mshtuko wa akili kama vile kuongezeka kwa utendaji au milipuko fupi ya utendaji usio wa kawaida wa magonjwa. Pia hutafuta mshtuko wa akili. "Tatizo ni kwamba haya yote ni matukio nadra sana", Terry anasema. Kwa hivyo, wataalamu wa matibabu huanza mchakato wa kuondoa sababu za kisaikolojia au za kimwili za mshtuko wa akili - kuangalia watu kwa vipindi virefu vya wakati, na kuongeza mkazo ambao unaweza kusababisha mshtuko wa akili, kama vile ukosefu wa usingizi, ili kupata ishara za kifafa. Terry na wenzake katika Neuronostics badala yake hutumia sekunde 20 za data isiyo na mshtuko kutoka kwa skani ya kawaida ya EEG. Kwa kutumia database ya rekodi za EEG kutoka kwa watu wenye na bila kifafa, watafiti wameunda mfano wa kompyuta ambao umejenga mtandao wa mwingiliano kati ya ishara zinazozalishwa na elektroni zilizowekwa kwenye kichwa kupima shughuli za ubongo, zinazoitwa njia za EEG. Mfano huu, Terry anaeleza, inaelezea "mabadiliko kati ya hali za msingi katika ubongo ambazo zinaonekana kuwa na afya, na hali kama za mshtuko ambazo zinaonekana kuwa za ugonjwa". Programu ya Neuronostics hutumia mfano huo kutengeneza alama ya hatari ambayo inaweza kusaidia daktari kutathmini hatari ya mtu binafsi ya kifafa. Kwa uchunguzi wa kawaida wa uchunguzi wa kwanza wa EEG, daktari anaweza kugundua kwa usahihi karibu 25% ya watu wenye kifafa. Utafiti wa Neuronostics unaonyesha kuwa inafanya vizuri zaidi, kugundua kifafa katika 60% ya wale walio na hali hiyo, na kufanya tathmini sahihi katika 87% ya kesi. Kuongeza kasi ya utambuzi wa kifafa kuna faida mbili kubwa. Kwanza, inaepuka uhitaji wa kupima kwa muda mrefu, na usumbufu unaohusiana na wale wanaochunguzwa. Kwa upande mwingine, inapunguza idadi ya mshtuko wa moyo ambao mtu anaweza kuwa nao - kuchelewesha kwa utambuzi na matibabu kunamaanisha kwamba mshtuko wa moyo utaendelea kutokea, na kwa ujumla, mtu anapoendelea kuwa na mshtuko wa moyo, inawezekana zaidi kuwa na mshtuko wa moyo. Ikiwa itathibitishwa kikamilifu, uwezo wa njia ya Neuronostics ya kushinda tafsiri za madaktari wa EEG za awali inaweza kuthibitika kuwa muhimu sana kwa utambuzi, anasema Davis. Kutolewa juu ya utambuzi Neuronostics<unk> mfumo imekuwa muda mrefu katika mimba. Terry na wenzake waliandika juu ya njia hiyo mwaka 2012. Terry kisha alizungumzia utafiti na mtaalamu wa teknolojia ya kibiashara katika Chuo Kikuu cha Exeter (ambapo Terry alikuwa basi msingi) ambaye alikuwa hisia na teknolojia na athari yake ya uwezekano. Chuo kikuu hicho kilijitolea kwa ulinzi wa hati miliki na, mnamo 2018, kilisaidia kuundwa kwa kampuni hiyo. Pia ilisaidia kupata mfululizo wa ruzuku ya serikali ya Uingereza - hivi karibuni, tuzo mbili za jumla ya £ 870,000 (US $ 1.2 milioni) mnamo Septemba 2020 kutoka Taasisi ya Kitaifa ya Utafiti wa Afya. Kampuni hiyo ilipata £ 300,000 katika raundi ya mbegu ya fedha. Sasa ina wafanyakazi wanne wa wakati wote na ni kuajiri, miongoni mwa majukumu mengine, mkuu wa masoko. Neuronostics inakadiria kuwa kuna soko la uwezekano la EEG milioni 3.5 kila mwaka nchini Marekani na Ulaya, na inapanga kulipa ada ya matumizi ya $ 400 nchini Marekani na sawa na $ 280 nchini Uingereza (kodi ni chini nchini Uingereza kwa sababu ya mahitaji chini ya udhamini wa serikali). Kampuni hiyo ilipokea idhini ya kisheria kwa BioNTech huko Ulaya na Uingereza mnamo Mei, na upanuzi wa Marekani umepangwa mwishoni mwa 2022. Hata hivyo, huenda utambuzi wa kifafa usiwe toleo lenye thamani zaidi la programu hiyo. "Kama matokeo, watafiti wanaweza kugundua uwezekano wa kuathiri kwa watu wanaotumia matibabu ya kifafa, ""anasema mwanahisabati Wessel Waldman, mwanzilishi mwenza na mkurugenzi wa kisayansi wa Neuronostics." Kwa kweli, ingawa baadhi ya wataalamu wa neva bado ni wasiwasi kuhusu uchambuzi wa EEG kwa ajili ya utambuzi, <unk> linapokuja utabiri, kuna <unk> mengi zaidi ya utambuzi kwamba mbinu za kompyuta kusaidia inaweza kweli kuchangia kitu muhimu<unk>, Woldman anasema. Karibu thuluthi moja ya watu wanaogunduliwa kuwa na kifafa hawapati faida yoyote kutokana na dawa yoyote inayopatikana. Kwa asilimia mbili ya wale waliobaki, inaweza kuchukua miezi mingi kupata matibabu yanayofaa. Uchunguzi wa neuroscience unaweza kuruhusu madaktari kuchunguza athari za dawa kwa haraka zaidi, ambayo inaweza kupunguza mshtuko na kupunguza matumizi ya dawa zenye athari kubwa za upande, anasema Woldman. Yeye ni kushirikiana na madaktari katika Hospitali ya St Vincent katika Fitzroy, Australia, mtihani mbinu. Matokeo ya mapema sana ni yenye kutia moyo, yeye asema. Neuronostics pia inaendeleza programu ya simu ya mkononi inayoitwa ConnectEP ambayo inafanya kazi na kizazi kipya cha vichwa vya sauti vya EEG visivyo na gharama kubwa, visivyo na gel vilivyobuniwa kwa matumizi ya nyumbani. Takwimu zinazotokana hazitakuwa za kiwango cha kliniki lakini bado zinaweza kuthibitika kuwa muhimu sana kwa wataalamu wa neva, Terry anasema. Kampuni hiyo inatarajia kutolewa kwa programu hiyo mwishoni mwa 2021. "Kizazi cha baadaye cha ConnectEP pia kinaweza kutoa utabiri muhimu wa muda mfupi wa hatari ya mshtuko wa moyo, uwezekano wa kuvutia, ""anasema Privett, ambaye anashiriki katika majaribio ya prototypes." Kwa ujumla, Privett anasema, athari ya uwezekano wa teknolojia ya Neuronostics kwa watu wenye kifafa ni kubwa. Kama inashughulikia teknolojia yake, Neuronostics inaendelea kuzingatia sana maoni kutoka kwa wadau wote katika matibabu ya kifafa - haswa wale walio na hali hiyo. "Ethos yetu", anasema Terry, "ni kuhakikisha kwamba mifano yetu na majaribio na kazi ya kliniki kuendeleza karibu sana pamoja".