Leading articles.

Influenza: Complications of the Nervous System, With Treatment

WILLIAM G. STEARNS, M. D., CHICAGO

Dr. T. Glover Lyon reports that physicians who had seen the epidemic of influenza in 1847 did not at first recognize the disease in 1889. In the descriptions of epidemic influenza written before 1889 the respiratory symptoms were made most prominent. Then the nervous, the gastrointestinal symptoms coming last. In 1889 the nervous symptoms were most striking. Then the respiratory and, lastly, the gastrointestinal. In 1892 and since, the gastrointestinal has equaled, if not surpassed, the respiratory symptoms in importance. The nervous symptoms still retain first rank. It was then only for a short period prior to 1889 that the nervous symptoms were not given the place of first importance. Whatever the relative importance of the nervous symptoms may be in influenza, it is certain that more organic and functional disturbances of the nervous system are produced by influenza than by any other acute infectious disease. The reason for this is found in Pfeiffer's bacillus and its mode of invasion, together with the unexplained selective action which the bacillus and its toxin have for nerve tissue.

1. Pfeiffer's bacillus, like pneumococci, gains entrance to the blood and metastatic inflammatory processes result, as encephalitis, meningitis.
2. Pfeiffer's bacillus is pyogenic; hence these metastatic foci may result in pulmonary and intracranial abscesses.
3. Pfeiffer's bacillus elaborates a toxin which, like the Klebs-Loeffler bacillus, produces toxic degenerative changes; for example, neuritis, etc.
4. Because of the general debilitating effect upon the entire organism, together with its selective enfeebling action upon the nervous system, the functional nervous and mental disorders are most numerous.

Nervous complications, in point of frequency ranking at least only second to the respiratory, are present at all times in the course of the disease, and often appear in their most dangerous forms late in convalescence. Of the prodromal period, the symptoms referable to the nervous system are, first and most constant, pain.

Pain.—Headache, usually frontal, orbital or supra-orbital; occasionally general; and at times occipital. Backache, usually lumbar. Pain in the legs, myalgia. The pain is often extreme, excruciating and occasionally accompanied by such great mental depression as to become overwhelming; the patient lies still, is stupid and unresponsive. This condition may pass into one of true coma. The excessive pain, however, may be shown by an opposite reaction. The patient becomes extremely restless, constantly agitated, making many wild demonstrative and often purposeless movements, and is usually more or less delirious, but rarely becomes maniacal. Usually these symptoms of profound mental and nervous toxemia greatly improve in from four to twelve hours, and quite largely disappear as the temperature rises, which in these cases reaches a high point.

Attacks have been reported as having been ushered in by cataleptic, epileptoid or apoplectic seizures, always followed by a few hours of unconsciousness. These symptoms of cortical irritation, too, pass away with the rising of the temperature. The nervous complications during the course of the disease are either inflammatory or degenerative, or both; that is, due either to the direct invasion of the bacillus or its toxins, or both.

1. Encephalitis occurs during the course of the disease or during convalescence, and is of two types—simple inflammatory or hemorrhagic, and purulent. Simple encephalitis is a rare complication and is due to the direct influence of the bacteria which are more or less disseminated throughout the encephalon, and to the effect of the toxins. The Pfeiffer bacilli have been found in the membranes, the cerebrospinal fluid, the brain substance, the capillaries and in the perivascular lymph spaces, as well as in foci of softening in both the cerebrum and cerebellum. The symptoms of encephalitis are both general and focal. The onset of the general symptoms may be slow and insidious, associated with vertigo and headache, or it may be a sudden apoplectiform seizure, usually preceded by chill, and the sudden rise of temperature. This latter mode of onset is most common, however, when it occurs during convalescence. There is loss of consciousness, coma, and usually convulsions. The focal symptoms depend wholly upon the location and severity of the lesions. In differentiating between encephalitis and hemorrhage, embolism and thrombosis, consider the acute onset with chill, constantly high temperature, the prevalence of an epidemic, and, if the patient be young, the age. The purulent form of encephalitis may be either primary, as proved by Oppenheim and Leichtenstern, or secondary, by extension from the cranial sinuses, or by metastasis from the suppurating tonsils, or purulent pulmonary foci.

2. Meningitis. Aside from the purulent meningitis resulting from direct extension from the cranial sinuses or other nearby foci, we have a much more common complication, often termed "meningitis grippalis, " in which there is primary invasion of the cerebrospinal membranes through an undemonstrated route, occurring usually at the height of the febrile course of the disease, most frequently found in children. The symptoms vary greatly, depending upon the location and severity of the inflammation. The differential diagnosis from epidemic cerebrospinal meningitis may be impossible to make, except by lumbar puncture.

3. Pseudo-meningitis. Beginning with headache, nausea and vomiting, high fever, somnolence and stupor; cervical rigidity and coma follows. Inequality and dilatation of the pupils; slow pulse and intermittent respiration; abdomen rarely retracted, warrants the diagnosis of meningitis. A few days later these symptoms disappear, and only those of influenza remain, and the diagnosis is pseudo-meningitis. Some of these cases have resulted fatally, and the autopsy revealed only edema of the membranes, increase in the cerebrospinal fluid, and hyperemia of the pia.

4. Myelitis. just as the brain may be invaded or poisoned by the bacteria or its toxin causing a varied symptomatology, determined by the location and severity of its lesions, so does the bacteria and its toxin affect and injure the spinal cord, producing any and all known spinal symptoms or groups of symptoms, combined in various ways. Myelitis may occur, together with encephalitis or meningitis. Myelitis due to influenza is always acute, and if very extensive and very acute the symptom group of Landry's paralysis may be reproduced. Paralyses, paraplegias, decubiti, cystic paralysis, sensory disturbances, ataxia and contractures may be a grouping of symptoms identical to compression transverse myelitis. Cases of spastic spinal paralysis have been reported. In these cases influenza appears to have selected and injured only the pyramidal tracts. Leyden has reported the case of a child, showing acute ataxia, in which the diagnosis of acute encephalo-myelitis was made, and yet recovery followed.

The nervous complications of convalescence are, aside from the occasional development of abscesses, chiefly toxic. The toxins of influenza, like those of other bacterial or chemical poisons, lead, alcohol, etc., if sufficiently virulent, will produce degenerative changes in the peripheral nerves, causing paralysis, anesthesia, etc. If the toxins are not sufficiently strong to resist or withstand the poisonous influence, then there arises only a disturbance in the function of those nerves or that nerve so affected, that is but transitory. Hence the toxic lesions of convalescence are either shown by loss of function or disordered function, or both. These lesions are, moreover, distributed so haphazard as to permit of no grouping or classifying. All of the chemical poisons and some of the bacterial toxins produce constant lesions, with characteristic symptom groups, but the influenza toxin shows little tendency to be selective in its attack upon the nerves, and that little is shown by a slightly more frequent affection of the cranial nerves.

The lesions due to degenerative changes are chiefly neuritis, multiple or polyneuritis, usually symmetrical, and consist of an acute inflammation of the nerve fibers. The onset appears from one to two weeks after the acute disease, and runs a comparatively short course, causing the usual clinical phenomena, with sensory and vasomotor symptoms most prominent, yet motor and trophic symptoms are not wanting.

5. Neuritis. While closely resembling the nerve degenerations following diphtheria as to frequency, course and recovery, yet it is decidedly unlike it in its distribution and consequently its clinical picture. While diphtheria is fairly constant in its selection of nerves, influenza has attacked almost every cranial nerve and spinal nerve in the body, often affecting only certain branches and singling out certain muscles or groups of muscles.

The olfactory, optic and ocular nerves are affected in all possible ways, even bilateral paralysis of the seventh nerve has been reported. Paralysis of the motor supply of the pharyngeal plexus is almost as common as after diphtheria. Angina pectoris has been reported. Attacks of syncope are not infrequent. Some cases of sudden death from paralysis of the heart are on record. Leyden has reported two cases of unilateral paralysis of the hypoglossal, both with and without paralysis of the corresponding half of the tongue. Vasomotor disturbances, often associated with vagus affections, are frequently indicated by hyperidrosis universalis; symmetrical asphyxia of the extremities, as in Raynaud's disease; general or localized hyperemia and erythema.

Many cases of neuritis affecting the spinal nerves have been reported affecting the nerves of the brachial plexus, with extensive atrophy. In these cases neuralgia was an especially prominent symptom. The ulnar, median and radial nerves have been affected in various combinations. Intercostal neuritis, with herpes zoster, has been of frequent occurrence. Isolated paralyses of the nerves of the lower extremities are not common, yet many cases have been reported.

Neuritis is often associated with the rheumatic affections of the fibrous tissues involving a single nerve or group of nerves. Branches of the sacral and the sciatic nerve are most often so affected, the lesion being primarily a perineuritis. Pain in these cases is most persistent, recovery the rule.

The symptoms due to irritative lesions are neuralgia, myalgia, convulsions, tremor and epilepsy. In many cases of epilepsy the first convulsion was noted during the course of influenza, and in many cases of epilepsy in which no seizure had taken place for many years the convulsions reappeared during its course.

Of the functional neuroses, neura-sthenia, and hysteria, like epilepsy, may appear for the first time during convalescence from influenza, or when previously present have reappeared or have been aggravated by an attack of influenza. These neuroses appear in every known type. In neurasthenia following influenza, hypochondria and motor weakness are most usually dominating symptoms.

Chorea is not very frequently developed in the course of influenza. However, a case of chorea, with spasms of glottis and diaphragm, has been observed in. a very young child, excluding the possibility of its being hysteria. As in croupous pneumonia, many cases of delirium tremens develop.

Influenza is given as an exciting or incidental factor in the production of most of the organic nervous diseases, as tabes dorsalis, paralysis agitans, spastic spinal paralysis, multiple sclerosis, Basedow's disease, general paresis, etc. Cramps, tremors, shaking paralysis of an arm, with anesthesia, and other similar symptoms of cortical irritation, are occasionally noted, with recovery.

6. Psychoses. Lichtenstern reports more psychoses after 439 cases of influenza than after 2,000 cases of typhoid fever and 3,000 cases of pneumonia combined. These were not the exhaustion psychoses, but rather of the toxic group, being due to the specific toxin of influenza, Many of these cases developed in the young, even in children. Kraepelin, on the other hand, believes a neuropathic or inherited base necessary to the development of a psychosis in the course of influenza. Psychoses often appear in the prodromal stage. For from one to three days before the temperature rises, the patient is affected with increasing depression, anxiety and stupor. These symptoms disappear upon the approach of the fever. The effects are transitory and toxic.

During the febrile stage, disturbances of consciousness, with hallucinations, melancholy, anxiety, fear, refusal of food, delusions of persecution, are not uncommon. Occasional cases of acute mania, with a wealth of delusions, hallucinations and illusions are noted. Recovery from these conditions usually take place with fall of temperature. During convalescence exhaustional psychoses occasionally develop. Aside from this form, none of the psychoses developing during this period have common characteristics, although they offer a tempting field for classification.

Treatment

The treatment of the nervous complications and sequelae of influenza, embracing, as it does, the greater part of the entire field of treatment of nervous and mental diseases, can not well be here discussed in detail. Each patient should be frequently observed and absolutely controlled from the first appearance of suspicious symptoms until convalescence has been established by at least two weeks. Aside from emphasizing the great importance of careful general management of every case, I want to call attention to a few old familiar drugs and their application to the treatment of the more severe nervous complications arising during the course of the disease.

In a few cases of influenza without respiratory or cardiac complications, in which varying degrees of irritation of the central nervous system were evidenced by excruciating pain, motor restlessness and mental agitation, as well as in several psychoses, I have used bromids freely, with apparent benefit and no untoward results. Dr. Ballinghall, in the British Medical Journal, 1904, most strongly recommends the use of potassium bromid in influenza. He has found the drug to have a sedative and even tonic action in neurotic and hysterical cases. He has found it especially efficient in cases in which the aching of the head and limbs were prominent symptoms, giving it in doses of ten to fifteen grains every two or three hours. He well cautions against the use of bromids in old patients, especially in those having pulmonary or cardiac complications.

The primary effect of the influenzal toxin upon the nervous system is always irritative, and the seeming prostration and nervous depression are but due to the benumbing and overwhelmingly irritative and paralyzing effect of the intoxication. The bromids are used to their greatest efficiency as a sedative in cases of systemic nervous irritation, and, as this is certainly the most commonly found condition in the nervous complications of influenza, its use should at least be given a thorough trial in these cases, where there are no complicating conditions contraindicating their use.

Opium or its derivatives is of great value also in these conditions of great nerve irritation, and is, in my opinion, indicated in every severe case and should be combined with bromids where that drug is not contraindicated.

In cases in which the action of the secretory and excretory organs are inhibited by the direct irritative action of poisons upon the central nervous system, opium in proper dosage will not increase that inhibitory influence, locking up the secretions more tightly, but it will, on the other hand, through its sedative action upon the central nervous system, destroy that inhibitive influence and allow the excretory organs to again become active. By preventing or counteracting the benumbing and paralyzing action of the bacterial poison on the central nervous system opium will increase the flow of secretions and excretions in such cases. The dryness of the mucous membranes will disappear, the digestive juices again begin their flow, the kidneys regain their activity, the skin become moist, and the constipation, where present, disappear. If calomel and soda be given with opium, there is added the needed diuretic and hepatic stimulation. Where the wet pack is properly used, it has by its sedative and eliminative action a most beneficial effect.

COMMENT.—In the treatment of this condition under these circumstances, in addition to the authoritative suggestions made by the writer, there are in each case certain indications which, to those of us who are experienced in the use of our specific remedies, suggest the prescribing of certain of these remedies. An early remedy for the influenza is gelsemium in full doses. For the nervous phenomena, the strontium bromid will meet the indications often; where the peripheral symptoms include circumscribed redness, rhus toxicodendron is of service. In certain of these cases, cactus will influence the terminal nerves exceedingly well, while it strengthens the heart and central nervous system. Macrotys is also indicated in some cases. With the best of treatment the results are not always satisfactory. The above excellent paper is timely and important. It was read by the doctor in Feb. before the Chicago Medical Society. Unfavorable results follow influenza oftener than we are apt to believe.

Ellingwood's Therapeutist, Vol. 2, 1908, was edited by Finley Ellingwood M.D.