Case report of rabies-induced persistent mental symptoms.

Rabies is a viral infection with a high case fatality rate. Typical symptoms of rabies include hydrophobia, pharynx muscle spasms, and progressive paralysis. Rabies-induced persistent mental disturbances are rare. Here we report a 22-year-old male who was infected with rabies after being attacked by a dog. He did not receive rabies vaccine immediately after the incident and was only provided with non-standard treatment at a local clinic. A week later he became disorientated, paranoid, and aggressive. One month after the attack, rabies antibody was found in his cerebrospinal fluid and a Magnetic Resonance Imaging (MRI) examination of his head revealed abnormal signals in the putamina, caudate nucleus, and insula. His mental symptoms persisted for six years and his daily functioning was severely impaired, but his vital signs were stable without signs of brain stem damage. Six years after the incident, a repeat MRI showed brain atrophy.

Case history

A 22-year-old male patient was brought to the hospital reporting psychological symptoms that had lasted for more than 6 years. He was bitten by a dog when he was 16 (in 2008) and developed fever, delirium, poor orientation, and confusion three days later. He was given antipyretic treatment at the local village clinic but was not given a rabies vaccine. One week after the incident, he began to show mental symptoms such as poor orientation, paranoia, and delirium. He could not recognize his family members and attacked his parents. One month after the incident, rabies antibody was found in his cerebrospinal fluid at a third tier  hospital. Routine laboratory tests showed no other abnormal results. Antiviral therapy was provided. His cranial Magnetic Resonance Imaging (MRI) results at the time are shown in Figure 1a: abnormal signals were found in his bilateral caudate nucleus, lenticular nucleus, and insula.

His mental symptoms persisted and severely affected his social functioning. At the time of the current admission (6 years after the incident), the patient showed low muscular tension of the limbs, normal muscle strength, tendon hyperreflexia, positive pathological reflexes of both lower limbs, unstable gait, and involuntary movements of the upper limbs. The patient wore dirty clothes and did not cooperate with the examination. He was agitated, acted inappropriately, and had slurred speech. He was not fully orientated to time and place and had difficulty concentrating on the interviewer’s questions. He had no apparent physical diseases and the family reported no history of allergies. He had normal vital signs (body temperature=37.3ºC, pulse= 89/min, breath=20/min, blood pressure=120/70mmHg) and no abnormal results were found from his physical examination. His four limbs showed no atrophy. He had a slightly elevated level of white blood cells but routine laboratory tests showed no other abnormality. Head MRI showed brain atrophy (Figure 1b). Based on the above results and his symptoms, he was diagnosed with residual mental symptoms due to rabies encephalitis.

Discussion

In China,rabies is more commonly seen in rural areas where people are more frequently exposed to domestic animals.[1,2] In these areas, local medical infrastructure is usually poor, so treatment is often not provided promptly. The incubation period of rabies is usually within three months. The length of the incubation period is related to age,the site of the wound (a shorter incubation period is seen for those who were bitten in the head or face), the depth of the wound,and the load and strength of the virus.[1] Non-thorough cleaning of the wound, other injuries, cold, and stress can also contribute to a shorter incubation period. After the incubation period, the typical clinical course of rabies, which usually lasts no longer than one month, can be divided into three stages.[3,4] (a) In the Prodromal Stage most patients have a fever, some have other flu-like symptoms,and many experience abnormal sensations around the wound such as numbing, pain, itching and formication. (b) In the Excitative Stage patients are hydrophobic and can show paroxysmal spasm of the pharyngeal muscle, difficulty breathing, difficulty urinating and defecating, hidrosis, and hydrostomia. And (c) in the Paralytic Stage patients become quiet and develop flaccid paralysis, particularly in the limbs; if facial muscles are be involved, this can cause irregular eye movements, mandible straining, mouth slacking, and lack of facial expression.

This patient’s initial symptoms were high fever and changes of consciousness followed by decreased muscular tension of the limbs without typical hydrophobic symptoms. His family members indicated that at the time of the original injury he was not given rabies vaccine. Approximately one month later, rabies antibody was found in his cerebrospinal fluid, confirming the diagnosis of rabies. In this case, however, the course of illness was atypical. The patient did not progress to the Excitative or Paralytic stage of rabies but, rather, continued to manifest mental symptoms of disorientation, disorganization, and unusual behavior. Six years after he was initially bitten, there was no improvement of his mental symptoms and his cranial MRI showed signs of brain atrophy, which is presumably secondary to rabies encephalitis. The primary damage was found in the insula, which can explain his mental symptoms. There were also abnormalities in the caudate nucleus and lenticular nucleus, which probably explain his extrapyramidal symptoms.

Rabies is currently prevalent in many places around the world, especially in underdeveloped areas where effective prevention and control methods are limited. Rabies is a disease with a high case fatality rate. After the central nervous system is infected, the subsequent encephalitis is often life-threatening. Once the rabies symptoms manifest, there is no effective treatment. However, as this case demonstrates, the clinical phenotypes of rabies can vary. This variability in presentation may cause misdiagnoses and delayed treatment - which can be fatal; so it is essential to be very careful in collecting the history of the early course of the condition.[5,6] For example,paralysis usually develops from the lower limbs and then spreads to respiratory muscles; a pattern of symptoms that can be confused with Guillain-Barré syndrome.[7,8] MRI may help find rabies at the early stages.[9,10] This case shows that mental symptoms may be the most prominent presenting symptoms, so psychiatrists and neurologists must always include rabies on the list of differential diagnoses they consider when evaluating new patients, particularly those from rural communities.