“I don’t know where I am,” said a terrified voice on the phone. It was the woman’s husband, and he was scared. “I’m lost,” he said in a panicked tone. It’s O.K., she told him, sounding as calm and reassuring as she could.
Her husband, a former high school English teacher in his 60s, left his mother-in-law’s that morning to return to their home several hours away in Pinon Hills, just north of San Bernardino, Calif. It was a route he drove often enough to know well. But after making his way through towns that seemed familiar, he lost his sense of how to get home. With her voice on the speakerphone, she guided him. His voice shook, and she knew he was crying. She wanted to cry, too, but forced herself to be the strength he needed. She still loved her husband, but he’d changed so much. Where was the man she married over 30 years ago?
An Earlier Diagnosis
Twenty years earlier, he found out he had multiple sclerosis. It started with numbness in his arms and hands. Sometimes his vision would darken on the periphery, as if he were in a tunnel. And then, after a couple of hours or so, he’d be fine.
He was referred to a local neurologist, who did some testing. An M.R.I. of his brain showed patchy white clouds among the normal gray swirls of brain. That finding was suggestive of multiple sclerosis. In M.S., the immune system goes awry and attacks the fatty sleeves that surround the nerves in the brain and spine; that’s what causes the characteristic M.R.I. findings. But it wasn’t a perfect fit. The fluid taken from his spine did not show the proteins that are usually seen in M.S. Moreover, while M.S. is characterized by episodes of unusual neurological symptoms that come and go, they usually last days or weeks rather than hours. Still, there are different forms of the disorder, and they can vary widely in symptom intensity and rate of progression. And there are few diseases that result in the M.R.I. findings and intermittent symptoms that this man had. Subsequent neurologists confirmed the diagnosis of M.S.
Even before he noticed the numbness in his arms, the man had frequent headaches, along with tunnel vision, so intense he’d vomit and have to spend the rest of the day in a darkened room. Could M.S. cause the headaches as well? Headaches like these were not usually seen in M.S., he was told. They were probably migraines.
As time went on, his disease looked less like M.S. He had strange personality changes: He became angry and aggressive in a way he’d never been. Over the years, that man his wife married, with his quiet humor and composure, nearly disappeared. Their two children, now teenagers, grew to fear his unpredictable and aggressive outbursts.
His behavior at school also became strange and volatile. The final straw was when, to make a point, he pulled a knife out of his back pocket and held it to the throat of a young male student. He was placed on disability leave.
His neurologists continued to treat him for M.S., but they also tested for other things. They found that his thyroid was fine; he had no nutritional deficiencies; it wasn’t syphilis or any other infection. Repeated M.R.I.s showed progression of the patchy white spots, but the reports always said that the findings were consistent with M.S. The patient tried the usual treatments for M.S. They didn’t help.
Losing His Way
Then he got lost driving home. At his next doctor’s appointment, they all agreed: He was too cognitively impaired to drive anymore. M.S. usually takes its toll on the body with a kind of rigid weakness and loss of coordination. But this patient’s disease seemed to target his thoughts and behavior.
His doctors heard of an experimental treatment at the Kaiser Permanente medical center in Los Angeles. Neurologists there were using a potent immune-suppressing medication to try to protect the nervous system from additional attacks and give it a chance to recover. His neurologist arranged for the patient to be seen there.
Dr. Brandon Beaber, a fellow in a branch of neurology specializing in diseases like M.S., was assigned to the patient. He introduced himself to the couple; he had already reviewed the man’s extensive records and had more questions. Your father died when you were young? he asked. The patient was a teenager when his father died, his wife explained when her husband seemed unable to answer. He had severe dementia and died of what was thought at the time to be arteriosclerosis. His mother died of breast cancer within a year. He had two brothers who both died in their 40s. It felt as if there was almost no family left — except for his children.
A Rare Disorder
“I don’t think you have M.S.,” the doctor said slowly. His symptoms, his M.R.I. and his family history suggested that he had a rare and newly described inherited disease called Cadasil. Beaber had seen a few cases of this unusual disorder. A report published in 1955 about two sisters who developed a severe dementia in early middle age is now thought to be the first described case. At the time, it was viewed as a variation of a type of dementia known as Binswanger’s disease, which can be associated with personality changes. In the earliest stages of the disease, the imaging looks like that seen in M.S. But we now know that patients with Cadasil often have the kind of severe headaches this patient described, as well as strokes and an early and relentlessly progressive dementia associated with often significant personality changes. Symptoms can start when patients are in their 30s. The diagnosis tends to be made a decade later.
The gene behind the disease was identified in 1993 — just a few years before this patient got his diagnosis of M.S. The genetic error affects the muscles in the small vessels in the brain, causing them to thicken, cutting blood flow to the segments of the brain they supply. In short, those who have Cadasil have thousands of tiny strokes that kill off the brain bit by bit. There are no treatments for the cognitive effects and no known cure for the disease.
Confirming a Gene Problem
Beaber sent the man for genetic testing. Cadasil and all its devastation are caused by a single error in a critical single link in a genome containing three billion otherwise normal links. Worse still, if he had it, then his children had a 50-50 chance of having inherited the same bad link. Testing showed he had Cadasil. Next they had to tell their two children that they might have it as well. It was, the man’s wife told me, the hardest thing she has ever done.
Over the next three years, the patient worsened. His world became smaller and smaller. He spoke less and less. He was unable to walk. He also lost his anger. His wife told me that toward the end, he actually seemed content. He spent his last few weeks surrounded by those who loved him, eating ice cream and watching baseball. She was grateful he never knew he was dying.
His two children decided to be tested for the gene. The news was devastating: Both have the gene. Their mother is amazed by their determination to lead full lives despite knowing what the future will bring. Both, however, have decided not to have children. Her son, now 29, had his first stroke nearly three weeks before his father died. It hasn’t stopped him from finishing his Ph.D. in psychology.
The patient’s wife wrote me a year after her husband died. This is a disease that leaves you powerless, she told me. This one gene error will steal from her all the people she loves most. The only power she has is to tell her husband’s story so that others who have this rare disease might be spared the long search for a diagnosis, and maybe, if they find out in time, they will have a chance to decide whether to have children who could carry this gene into yet another generation of suffering.B:
三中三聪明算【唐】【栀】【这】【话】【说】【的】【声】【音】【不】【大】，【但】【以】【叶】【宁】【笙】【的】【修】【为】，【肯】【定】【是】【听】【的】【很】【清】【楚】【的】，【他】【诧】【异】【会】【从】【唐】【栀】【口】【中】【听】【到】【吃】【醋】【这】【两】【个】【字】。 【叶】【城】【说】【过】，【如】【果】【一】【个】【女】【人】【因】【为】【你】【而】【吃】【醋】，【那】【她】【一】【定】【很】【喜】【欢】【你】，【很】【在】【乎】【你】。 【他】【顿】【时】【高】【兴】【了】，【先】【前】【不】【给】【饭】【吃】【还】【差】【点】【要】【被】【打】【断】【腿】【的】【事】【情】，【都】【被】【抛】【到】【九】【霄】【云】【外】【去】【了】。 “【你】【吃】【我】【的】【醋】？” “【不】【然】【呢】？
【然】【后】【就】【离】【开】【了】 【呆】【在】【原】【处】【的】【汀】【兰】，【还】【是】【没】【忍】【住】，【落】【下】【了】【眼】【角】【的】【泪】【水】。 【谁】【比】【谁】【应】【该】，【谁】【又】【有】【什】【么】【不】【应】【该】，【都】【是】【心】【甘】【情】【愿】，【怪】【不】【得】【旁】【人】。 【又】【过】【了】【一】【天】，【长】【宁】【的】【身】【子】【确】【实】【是】【好】【了】【不】【少】，【但】【还】【是】【会】【做】【梦】，【在】【梦】【里】【还】【是】【会】【说】【些】【胡】【话】，【表】【情】【很】【是】【痛】【苦】，【还】【烧】【是】【退】【的】【干】【净】【了】，【人】【也】【精】【神】【了】【许】【多】，【只】【是】【眼】【底】【有】【些】【黑】【黑】【的】，【像】【是】【没】
“【好】【重】！” 【在】【中】【拳】【的】【瞬】【间】，【小】【鲁】【伊】【兹】【只】【有】【这】【一】【个】【念】【头】，【然】【后】【整】【个】【人】【完】【全】【陷】【入】【了】【黑】【暗】【之】【中】。 “【嘭】！” 【小】【鲁】【伊】【兹】【重】【重】【地】【倒】【在】【了】【拳】【台】【上】，【发】【出】【沉】【重】【的】【撞】【击】【声】【音】。 【这】【声】【音】，【通】【过】【音】【响】【的】【放】【大】，【再】【度】【将】【所】【有】【人】【人】【吓】【了】【一】【跳】，【全】【身】【都】【是】【一】【激】【零】。 “【嚯】……【嚯】……” 【赵】【烈】【急】【喘】【两】【下】，【一】【边】【看】【着】【已】【经】【陷】【入】【昏】【迷】【的】
【柳】【修】【听】【了】【一】【脸】【肯】【定】【的】【点】【了】【点】【头】：“【爹】，【我】【都】【确】【认】【清】【楚】【了】【的】，【不】【会】【有】【错】。” 【柳】【怀】【志】【听】【了】，【目】【光】【看】【向】【旁】【边】【的】【炎】【祁】：“【炎】【谷】【主】【怎】【么】【看】【这】【件】【事】？” 【炎】【祁】【听】【了】，【倒】【是】【满】【脸】【淡】【淡】【笑】【笑】：“【柳】【门】【主】【难】【道】【还】【看】【不】【明】【白】，【照】【刚】【刚】【的】【情】【形】【看】，【那】【个】【叫】【阿】【初】【的】【很】【明】【显】【跟】【紫】【昆】【山】，【跟】【伏】【宗】【主】【是】【有】【关】【系】【的】，【若】【真】【是】【如】【大】【家】【猜】【测】，【是】【伏】【宗】【主】【流】【落】
【兽】【人】【大】【军】【走】【得】【非】【常】【的】【干】【净】【利】【落】，【让】【天】【风】【联】【盟】【的】【众】【人】【感】【到】【非】【常】【的】【不】【可】【思】【议】。 【当】【下】【了】【游】【戏】【之】【后】，【林】【萧】【主】【动】【联】【系】【上】【李】【天】【琦】【时】，【他】【才】【知】【道】【是】【因】【为】【什】【么】【原】【因】【了】。 【原】【来】【是】【林】【萧】【一】【个】【命】【令】【直】【接】【将】【兽】【人】【军】【团】【给】【调】【回】【去】【的】。 【林】【萧】【的】【意】【思】【很】【明】【确】，【那】【就】【是】【鹰】【蹄】【帝】【国】【现】【在】【的】【主】【要】【敌】【人】【是】【宁】【远】【的】【神】【鹰】【帝】【国】，【所】【以】【他】【希】【望】【李】【天】【琦】【能】【够】【克】【制】三中三聪明算【阿】【不】【福】【思】【落】【座】【以】【后】，【感】【觉】【到】【刚】【才】【的】【瞬】【间】【自】【己】【仿】【佛】【是】【一】【个】【客】【人】【一】【样】。 【加】【菲】【的】【气】【场】【实】【在】【是】【太】【强】【了】，【阿】【不】【福】【思】【如】【果】【不】【是】【生】【性】【洒】【脱】【一】【些】【再】【加】【上】【一】【些】【特】【殊】【的】【心】【里】【情】【况】【的】【加】【持】【也】【许】【跟】【着】【加】【菲】【很】【难】【做】【到】【如】【今】【的】【这】【种】【基】【本】【平】【等】【的】【对】【话】。 【想】【想】【自】【己】【的】【哥】【哥】【与】【加】【菲】【谈】【笑】【风】【生】【的】【样】【子】，【哥】【哥】【就】【是】【哥】【哥】，【弟】【弟】【就】【是】【弟】【弟】，【果】【然】【自】【己】【还】【是】【与】【他】
【秦】【杰】【的】【思】【绪】【在】【王】【秋】【的】【话】【语】【中】【紊】【乱】，【他】【又】【沉】【浸】【到】【了】【那】【个】【不】【堪】【回】【首】【的】【过】【往】【当】【中】。 ‘【朴】【教】【练】，【我】【加】【入】【战】【队】【的】【申】【请】【书】【您】【看】【了】【吗】？’【朴】【易】【辉】【是】MT【战】【队】【的】【任】【职】【教】【练】，【在】MT【战】【队】【里】【面】【权】【利】【巨】【大】，【可】【以】【随】【意】【地】【决】【定】【任】【何】【选】【手】【的】【职】【业】【命】【运】。 ‘【我】【看】【了】，【写】【的】【不】【错】。【但】【要】【不】【要】【你】【加】【入】【战】【队】【不】【是】【我】【说】【了】【能】【算】【的】，【一】【切】【得】【看】【老】【板】【的】【意】【思】
“【怎】【么】？【你】【是】【不】【是】【很】【好】【奇】，【我】【父】【汗】【一】【直】【在】【柔】【然】【馆】，【今】【日】【怎】【么】【出】【现】【在】【了】【这】【里】？” 【茹】【茹】【公】【主】【看】【了】【高】【小】【欢】【一】【眼】，【有】【些】【得】【意】【的】【显】【摆】。 【不】【等】【高】【小】【欢】【开】【口】，【茹】【茹】【公】【主】【已】【经】【冷】【笑】【道】：“【大】【魏】【天】【下】，【刘】【腾】【元】【叉】【虽】【然】【混】【账】【可】【是】【还】【不】【糊】【涂】，【他】【们】【一】【直】【派】【人】【盯】【紧】【了】【柔】【然】【馆】，【可】【刘】【腾】【元】【叉】【一】【死】，【剩】【下】【的】【皇】【帝】【元】【诩】【和】【胡】【灵】【太】【后】【相】【斗】，【他】【们】【的】【目】
“【小】【子】，【你】【很】【走】【运】，【能】【见】【到】【我】【的】【片】【面】【族】【人】！”【魔】【猎】【才】【站】【在】【非】【常】【前】【面】，【黑】【沉】【沉】【说】【道】。 【林】【天】【当】【今】【再】【奈】【何】【接】【洽】【也】【不】【会】【将】【当】【前】【这】【个】【傻】【子】【和】【以】【前】【那】【俊】【秀】【的】【狗】【神】【族】【少】【年】【接】【洽】【在】【一】【路】，【这】【真】【的】【是】【极】【大】【的】【反】【差】，【而】【当】【今】【确】【凿】【确】【凿】【产】【生】【在】【本】【人】【的】【当】【前】，【不】【得】【不】【使】【人】【信】【赖】。 【林】【天】【当】【今】【思】【量】【的】【是】【若】【何】【在】【这】【么】【多】【的】【傻】【子】【中】【逃】【出】【去】，【保】【住】【本】【人】